Phenylpiracetam

Phenylpiracetam (Fonturacetam) is a potent synthetic nootropic in the racetam family, developed in Russia, that may enhance cognitive function, physical performance, and cold tolerance at doses of 100-200 mg, 2-3 times daily. Research suggests benefits for attention, memory, and psychomotor function, though it’s banned by WADA for competitive sports.

Alternative Names: Fonturacetam, Carphedon, Phenotropil, (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide

Categories: Nootropic, Racetam, Cognitive Enhancer, Psychostimulant

Primary Longevity Benefits


  • Cognitive enhancement
  • Psychomotor stimulation
  • Increased physical performance
  • Cold tolerance

Secondary Benefits


  • Neuroprotection
  • Antidepressant effects
  • Anticonvulsant properties
  • Recovery from brain injuries

Mechanism of Action


Phenylpiracetam ((RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide) exerts its potent cognitive-enhancing and psychostimulant effects through multiple complementary mechanisms that distinguish it from other members of the racetam family. As a phenylated derivative of piracetam, the addition of a phenyl ring at the 4-position of the pyrrolidone nucleus confers unique pharmacodynamic properties that contribute to its reportedly 30-60 times greater potency compared to the parent compound. The most distinctive aspect of phenylpiracetam’s mechanism involves its direct interaction with monoaminergic neurotransmitter systems, a property largely absent in other racetams. Phenylpiracetam demonstrates significant affinity for dopamine transporters (DAT), functioning as a mild dopamine reuptake inhibitor.

This action increases synaptic dopamine levels in key brain regions including the prefrontal cortex, striatum, and nucleus accumbens. The R-isomer appears particularly potent in this regard, while the S-isomer shows more selective effects. This dopaminergic enhancement contributes substantially to phenylpiracetam’s stimulant-like properties, including increased motivation, alertness, and psychomotor activation. Additionally, phenylpiracetam modulates noradrenergic transmission, both through mild norepinephrine reuptake inhibition and potential direct interactions with adrenergic receptors.

This noradrenergic activity contributes to the compound’s effects on attention, arousal, and physical performance. Phenylpiracetam also demonstrates affinity for nicotinic acetylcholine receptors, particularly the α4β2 and α7 subtypes, enhancing cholinergic transmission in brain regions critical for cognitive function. This cholinergic modulation complements the monoaminergic effects, creating a balanced profile of cognitive enhancement and stimulation. Beyond neurotransmitter modulation, phenylpiracetam influences neuronal membrane structure and function.

Like other racetams, it interacts with the polar head groups of membrane phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine, enhancing membrane fluidity and stability. This membrane modulation affects numerous processes including receptor sensitivity, ion channel function, and signal transduction. The phenyl ring substitution appears to enhance these membrane interactions, potentially explaining phenylpiracetam’s greater potency compared to piracetam. The membrane effects create a foundation for enhanced synaptic transmission and neuroplasticity, particularly under conditions of stress or neuronal damage.

A crucial aspect of phenylpiracetam’s mechanism involves its effects on cerebral metabolism and energy utilization. The compound enhances glucose uptake and metabolism in neuronal tissues through multiple mechanisms: increased expression and activity of glucose transporters, enhanced glycolytic enzyme activity, and optimized mitochondrial function. This metabolic enhancement is particularly pronounced under conditions of hypoxia, hypothermia, or metabolic stress, where phenylpiracetam helps maintain ATP production and energy charge. The compound also increases cerebral blood flow, improving oxygen and nutrient delivery to neuronal tissues.

These metabolic effects provide the energetic foundation for enhanced cognitive and physical performance, particularly under challenging conditions. Phenylpiracetam demonstrates remarkable neuroprotective properties through multiple mechanisms. It reduces oxidative stress by enhancing endogenous antioxidant systems, including superoxide dismutase and glutathione peroxidase, while directly scavenging certain free radical species. The compound also attenuates excitotoxicity by modulating calcium homeostasis and reducing excessive glutamate receptor activation under pathological conditions.

Additionally, phenylpiracetam upregulates brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression, promoting neuronal survival, differentiation, and plasticity. These neuroprotective mechanisms are particularly relevant for phenylpiracetam’s applications in recovery from traumatic brain injury, stroke, and neurodegenerative conditions. A distinctive feature of phenylpiracetam involves its effects on gene expression related to stress adaptation. The compound modulates the expression of heat shock proteins and other molecular chaperones that protect cellular proteins under conditions of stress.

It also influences the expression of genes involved in cellular energy metabolism, antioxidant defense, and neuroplasticity. This genomic modulation contributes to phenylpiracetam’s adaptogenic properties, enhancing resilience to various stressors including physical exertion, cold exposure, and psychological stress. The stereochemistry of phenylpiracetam significantly influences its mechanism of action. The compound exists as R- and S-enantiomers, with the racemic mixture typically used clinically.

The R-isomer demonstrates greater affinity for dopamine transporters and more pronounced psychostimulant effects, while the S-isomer shows more selective metabolic effects and potentially greater neuroprotective properties. This stereoselectivity creates opportunities for tailored applications of specific enantiomers for different therapeutic goals. The pharmacokinetics of phenylpiracetam contribute significantly to its mechanism of action. As a moderately lipophilic compound with excellent blood-brain barrier penetration, phenylpiracetam achieves effective concentrations in the central nervous system relatively quickly, with peak plasma levels occurring 0.5-1 hour after administration.

The compound demonstrates linear pharmacokinetics and moderate protein binding, allowing for predictable dose-response relationships. Phenylpiracetam’s elimination half-life of 3-5 hours is similar to piracetam’s, necessitating multiple daily dosing for sustained effects. The compound undergoes partial hepatic metabolism, with both unchanged drug and metabolites excreted in urine. The complex, multi-target mechanism of phenylpiracetam explains its diverse cognitive, physical, and adaptogenic effects.

The combination of monoaminergic modulation, membrane effects, metabolic enhancement, neuroprotection, and genomic regulation creates a comprehensive approach to enhancing performance and resilience. This mechanistic complexity also explains phenylpiracetam’s balanced profile, providing significant stimulation and cognitive enhancement without the pronounced side effects associated with traditional stimulants. The phenyl ring substitution that distinguishes phenylpiracetam from piracetam appears to confer both enhanced lipophilicity and specific binding properties for monoaminergic targets, explaining its substantially greater potency and distinct pharmacological profile compared to the parent compound.

Optimal Dosage


Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.

100-200 mg per day, typically divided into 1-2 doses. The higher end of this range (200 mg) is often used for cognitive enhancement, while lower doses (100 mg) may be sufficient for general neuroprotective effects.

By Condition

Condition Dosage Notes
Cognitive enhancement 100-200 mg, 1-2 times daily Often taken 30-60 minutes before mentally demanding tasks. Effects typically onset within 30-60 minutes and may last 4-6 hours. Some users report diminishing returns above 200 mg per dose.
Physical performance 100-200 mg, taken 60-90 minutes pre-workout Used to enhance endurance, cold tolerance, and physical stamina. Banned by the World Anti-Doping Agency (WADA) for competitive athletes.
Post-stroke recovery 100 mg, 2-3 times daily Used in medical settings in Russia and some Eastern European countries. This application should only be under medical supervision.
Asthenia (weakness/fatigue) 100-200 mg in the morning Often used as a single morning dose to combat fatigue without disrupting sleep. May be combined with a second early afternoon dose if needed.
Cognitive decline 100 mg, 1-2 times daily Used in some countries as an adjunct therapy for age-related cognitive decline. Should be used under medical supervision for this application.

By Age Group

Age Group Dosage Notes
Adults (18-65 years) 100-200 mg daily Start with lower doses (50-100 mg) to assess individual tolerance and sensitivity.
Older adults (65+ years) 50-100 mg daily Start at the lower end of the dosage range and increase gradually if needed. Increased sensitivity possible; monitor for side effects.
Children and adolescents (under 18 years) Not recommended Safety and efficacy not established in pediatric populations.

Frequency Recommendations

Optimal Frequency: Most users report best results with non-daily use, such as 2-3 times per week, or following a cycle of 1-2 weeks on followed by 1 week off.

Timing: Morning dosing is typically preferred to avoid potential sleep disruption. For cognitive enhancement, taking 30-60 minutes before mentally demanding tasks provides optimal timing.

Cycling Protocol: Common cycling protocols include: 1) 2-3 days per week (e.g., Monday/Wednesday/Friday); 2) 5 days on, 2 days off; 3) 2 weeks on, 1 week off. These approaches may help minimize tolerance development.

Tolerance Management: Tolerance to phenylpiracetam’s effects may develop relatively quickly with daily use. Cycling, maintaining the lowest effective dose, and occasional breaks from supplementation are recommended strategies.

Special Populations

Liver Impairment: Start with reduced doses (50-100 mg) and monitor closely; phenylpiracetam undergoes partial hepatic metabolism

Kidney Impairment: Use with caution and consider reduced dosing; limited data on pharmacokinetics in renal impairment

Pregnancy Breastfeeding: Avoid use due to insufficient safety data

Hypertension: Monitor blood pressure; some users report mild increases in blood pressure

Epilepsy: Use with caution; theoretical potential to lower seizure threshold based on mechanisms affecting neurotransmitter systems

Anxiety Disorders: Start with lower doses (50-100 mg); may exacerbate anxiety in sensitive individuals

Administration Guidance

With Food: Can be taken with or without food. Some users report reduced gastrointestinal discomfort when taken with food, though absorption may be slightly delayed.

Water Consumption: Ensure adequate hydration (at least 8 oz of water) when taking phenylpiracetam.

Powder Vs Capsules: Available in both forms. Powder allows for more precise dosing but has a bitter taste; capsules offer convenience and mask the taste.

Sublingual: Some users report faster onset with sublingual administration, though the bitter taste is significant. Limited data on bioavailability differences compared to oral administration.

Storage: Store in a cool, dry place away from direct light. Phenylpiracetam is relatively stable but may degrade with prolonged exposure to heat, moisture, or light.

Combination Strategies

With Choline Sources

  • May enhance effects and potentially reduce headaches reported by some users
  • Alpha-GPC (300-600 mg) or CDP-Choline (250-500 mg)
  • Take simultaneously with phenylpiracetam
  • Not all users require additional choline supplementation; consider adding only if experiencing headaches

With Other Nootropics

  • L-theanine (100-200 mg) for smoother effects; Bacopa monnieri for complementary memory benefits
  • Avoid combining with stimulants or other compounds that affect dopamine systems without careful consideration
  • Start with phenylpiracetam alone before adding other compounds to better assess individual effects

Research Limitations

Most dosage recommendations are based on limited clinical research, primarily from Russia and Eastern Europe where phenylpiracetam is used medically, along with anecdotal reports and extrapolation from pharmacological principles. Individual responses vary significantly based on genetics, metabolism, and concurrent supplements or medications. The optimal dosage for specific applications may differ substantially between individuals, necessitating a personalized approach starting with lower doses.

Bioavailability


Absorption Rate

Phenylpiracetam demonstrates good oral bioavailability, estimated at 100% in animal studies, though precise human data is limited. The addition of the phenyl ring to the piracetam structure enhances lipophilicity, allowing for improved blood-brain barrier penetration compared to piracetam. Absorption occurs primarily in the small intestine, with peak plasma concentrations typically reached within 1 hour of oral administration.

Pharmacokinetics

Onset Of Action

  • 30-60 minutes
  • 60-90 minutes
  • Individual variations in metabolism and neurochemistry may affect onset time

Peak Plasma Time

  • 30-60 minutes
  • 60-120 minutes
  • Food may slightly delay absorption but does not significantly reduce overall bioavailability

Half Life

  • 3-5 hours
  • 4-6 hours for cognitive effects; up to 8-10 hours for physical performance enhancement
  • The duration of subjective effects may not directly correlate with plasma half-life due to downstream neurochemical changes

Metabolism

Primary Pathway: Phenylpiracetam undergoes limited metabolism, with approximately 40% hydroxylated in the liver and 60% excreted unchanged in urine.

Metabolites: The primary metabolite is 4′-hydroxy-phenylpiracetam, which may retain some activity, though less than the parent compound.

Enzymes Involved: Specific cytochrome P450 enzymes responsible for hydroxylation have not been fully characterized, but likely include CYP2D6 based on structural considerations.

Excretion: Primarily renal excretion, with approximately 60% excreted unchanged in urine and 40% as metabolites. Complete elimination typically occurs within 24 hours.

Blood Brain Barrier Penetration

Phenylpiracetam readily crosses the blood-brain barrier due to its enhanced lipophilicity compared to piracetam. The addition of the phenyl ring significantly improves CNS penetration, with brain concentrations reaching approximately 40-60% of plasma concentrations in animal studies. This improved BBB penetration is a key factor in its greater potency compared to piracetam, requiring substantially lower doses for comparable effects.

Stereochemistry

Isomers: Phenylpiracetam contains a chiral center and exists as R and S enantiomers. Commercial products typically contain the racemic mixture (equal parts of both enantiomers).

Enantiomer Differences: The R-enantiomer (carphedon) appears to be primarily responsible for the nootropic and neuroprotective effects, while the S-enantiomer may contribute more to physical performance enhancement.

Notes: Some research suggests the R-enantiomer has greater affinity for specific brain receptors, though both enantiomers are pharmacologically active.

Factors Affecting Bioavailability

Factor Impact Notes
Food intake Taking phenylpiracetam with food may delay absorption by 30-60 minutes but does not significantly reduce overall bioavailability. High-fat meals may slightly enhance absorption due to increased bile secretion, though the effect is modest.
Age Older adults may experience altered pharmacokinetics due to changes in body composition, hepatic function, and renal clearance. Reduced dosing may be appropriate in elderly populations, starting at 50-100 mg rather than 100-200 mg.
Liver function Impaired hepatic function may reduce metabolism of the portion (approximately 40%) that undergoes hydroxylation. Dose reduction may be warranted in individuals with significant liver impairment.
Kidney function Reduced renal function may lead to decreased clearance and potential accumulation, as approximately 60% is excreted unchanged in urine. Dose reduction and/or extended intervals between doses may be appropriate in individuals with significant kidney impairment.
Genetic variations Polymorphisms in genes encoding drug transporters or metabolizing enzymes may affect individual response. Limited specific data on genetic factors affecting phenylpiracetam pharmacokinetics, but individual variation in response is observed clinically.

Enhancement Methods

Timing Recommendations

For cognitive enhancement, phenylpiracetam is best taken 30-60 minutes before mentally demanding tasks to align peak effects with performance demands. Morning dosing is typically preferred to avoid potential sleep disruption, though early afternoon dosing is generally well-tolerated if needed for afternoon cognitive tasks. For physical performance enhancement, taking 60-90 minutes pre-workout allows for optimal timing of effects. Taking on an empty stomach may provide slightly faster onset, though taking with food is acceptable if gastrointestinal comfort is a concern.

If using multiple daily doses, spacing them at least 4-6 hours apart helps maintain more consistent effects throughout the day.

Tissue Distribution

Phenylpiracetam distributes widely throughout body tissues, with particular affinity for brain tissue due to its lipophilicity. Animal studies suggest accumulation in the cerebral cortex, hippocampus, and striatum – areas associated with cognition, memory, and motor function. The volume of distribution is moderate, estimated at 0.6-0.8 L/kg, indicating distribution beyond plasma into tissues. Unlike some compounds, phenylpiracetam does not appear to accumulate significantly in adipose tissue, contributing to its relatively predictable pharmacokinetic profile.

Research Limitations

Human pharmacokinetic data for phenylpiracetam is limited, with most information derived from Russian and Eastern European research, some of which is not readily accessible in English-language scientific literature. Animal studies provide valuable insights but may not perfectly translate to human pharmacokinetics. Individual variations in absorption, metabolism, and response are substantial but incompletely characterized. The pharmacokinetics of individual enantiomers and their specific contributions to various effects require further investigation.

Safety Profile


Safety Rating i

3Moderate Safety

General Safety Overview

Phenylpiracetam has a generally favorable safety profile when used at recommended doses by healthy individuals. It has been used medically in Russia and some Eastern European countries for decades with a relatively low incidence of serious adverse effects. However, its safety profile is not as extensively documented as many approved pharmaceuticals in Western countries, with limited long-term safety data from large-scale clinical trials. The compound appears to have a wide therapeutic window, with toxicity occurring at doses far above therapeutic ranges.

Most side effects are mild and transient, though individual sensitivity varies considerably.

Side Effects

Common Side Effects:

Effect Prevalence Severity Notes
Insomnia or sleep disturbances Common (10-15%) Mild to moderate More likely with evening dosing or in sensitive individuals; typically resolves by avoiding late-day administration
Headache Common (10-15%) Mild to moderate May be related to cholinergic effects; often responsive to adequate hydration or supplemental choline
Irritability or agitation Common (5-10%) Mild to moderate More common at higher doses or in anxiety-prone individuals
Gastrointestinal discomfort Uncommon (3-8%) Mild Typically mild nausea or stomach discomfort; often improved by taking with food
Increased blood pressure Uncommon (3-8%) Mild to moderate Typically modest elevations; more significant in individuals with pre-existing hypertension

Less Common Side Effects:

Effect Prevalence Severity Notes
Anxiety Uncommon (2-5%) Mild to moderate More common in individuals with pre-existing anxiety disorders or at higher doses
Dizziness Uncommon (2-5%) Mild Typically transient; may be related to blood pressure changes
Dry mouth Uncommon (2-5%) Mild May be related to sympathomimetic effects
Increased heart rate Uncommon (2-5%) Mild Typically modest increases; more significant in sensitive individuals
Mild tremor Rare (1-2%) Mild More common at higher doses

Rare But Serious Side Effects:

Effect Prevalence Severity Notes
Significant hypertension Very rare (<1%) Moderate to severe Risk increased in individuals with pre-existing hypertension or cardiovascular conditions
Allergic reactions Very rare (<1%) Mild to severe May include skin rashes, itching, or more serious hypersensitivity reactions
Psychomotor agitation Very rare (<1%) Moderate to severe More likely at high doses or in sensitive individuals
Seizures Extremely rare (<0.1%) Severe Primarily theoretical risk based on mechanism; case reports extremely limited

Contraindications

Condition Recommendation Rationale
Severe hypertension Avoid use Potential to increase blood pressure may exacerbate existing hypertension
Severe anxiety disorders Avoid use or use with extreme caution at low doses Stimulatory effects may worsen anxiety symptoms
Seizure disorders Avoid use Theoretical potential to lower seizure threshold based on effects on neurotransmitter systems
Severe cardiovascular disease Avoid use Potential cardiovascular effects may pose risks in compromised individuals
Psychosis or severe psychiatric disorders Avoid use Stimulatory and dopaminergic effects may potentially exacerbate symptoms
Pregnancy and breastfeeding Avoid use Insufficient safety data; potential risks to fetal development or infant health
Children and adolescents (under 18 years) Avoid use Insufficient safety data; developing nervous system may be particularly vulnerable
Severe renal impairment Avoid use or use with caution at reduced doses Primarily eliminated through kidneys; impaired clearance may lead to accumulation
Severe hepatic impairment Use with caution at reduced doses Partially metabolized in liver; impaired metabolism may affect clearance

Drug Interactions

Medication Class Interaction Type Severity Mechanism Management Examples
Stimulants Potentially additive stimulant effects Moderate Combined effects on dopamine, norepinephrine, and other neurotransmitter systems Avoid combination or use with extreme caution at reduced doses of both agents Amphetamines, methylphenidate, modafinil, high-dose caffeine
Antihypertensives Potential reduction in antihypertensive efficacy Mild to moderate Phenylpiracetam’s modest pressor effects may counteract blood pressure-lowering medications Monitor blood pressure if combination necessary; may require adjustment of antihypertensive dosing Beta-blockers, ACE inhibitors, calcium channel blockers
MAO Inhibitors Potentially dangerous interaction Moderate to severe Combined effects on monoamine systems may lead to hypertensive crisis or serotonin syndrome Avoid combination Phenelzine, tranylcypromine, selegiline at higher doses
Anticonvulsants Potential reduction in seizure threshold Mild to moderate Theoretical concern based on phenylpiracetam’s effects on neurotransmitter systems Avoid combination in patients with seizure disorders; use with caution in others Phenytoin, carbamazepine, valproate
Anticoagulants/Antiplatelets Theoretical concern for altered effects Unknown; likely mild Limited data; potential for altered metabolism or effects on platelet function Monitor closely if combination necessary; consider alternative nootropics Warfarin, clopidogrel, aspirin
Thyroid medications Potential for additive stimulatory effects Mild Combined sympathomimetic-like effects Monitor for excessive stimulation; adjust dosing if necessary Levothyroxine, especially if dosing results in subclinical hyperthyroidism

Supplement Interactions

Supplement Interaction Type Severity Mechanism Management Notes
Choline sources (Alpha-GPC, CDP-Choline) Generally beneficial synergistic interaction Positive Supports acetylcholine synthesis which may complement phenylpiracetam’s effects Common intentional combination; typically well-tolerated May reduce headaches associated with phenylpiracetam use in some individuals
Stimulant herbs (Yohimbe, Bitter Orange) Potentially additive stimulant effects Mild to moderate Combined effects on catecholamine systems Avoid combination or use with caution at reduced doses May increase risk of cardiovascular side effects
Other racetams Potentially additive effects Mild Similar mechanisms affecting cholinergic and glutamatergic systems If combining, reduce doses of both compounds; not typically necessary to combine Limited advantage to combining multiple racetams
Caffeine Additive stimulant effects Mild to moderate Different but complementary mechanisms of CNS stimulation Reduce caffeine intake when using phenylpiracetam; be cautious with high doses of both Common unintentional combination that may increase side effects

Tolerance And Dependence

Tolerance Development:

  • Moderate; typically develops within 1-2 weeks of daily use
  • Likely involves adaptation of neurotransmitter systems, particularly dopaminergic pathways
  • Cycling use (e.g., 2-3 times weekly or 2 weeks on/1 week off) can minimize tolerance development

Psychological Dependence:

  • Low to moderate
  • Individuals with history of substance use disorders or addictive tendencies
  • Craving, anxiety when unable to use, continued use despite adverse effects

Physical Dependence:

  • Very low
  • Rarely reported; may include fatigue, decreased motivation, or mild depression upon discontinuation after prolonged use
  • True physical dependence is uncommon but psychological dependence may manifest with physical symptoms

Long Term Safety

Clinical Experience: Used medically in Russia and some Eastern European countries for decades with relatively few reports of serious long-term adverse effects

Animal Studies: Limited evidence of toxicity in rodent studies at therapeutic doses; safety margin appears substantial

Research Limitations: Limited long-term controlled studies in Western medical literature; most long-term data comes from Russian medical practice and literature

Theoretical Concerns: Potential for neurotransmitter system adaptations with chronic use; significance and reversibility unclear

Monitoring Recommendations: For long-term use, periodic assessment of blood pressure, heart rate, sleep quality, and mood is prudent

Overdose Information

Symptoms:

  • Severe agitation
  • Significant hypertension
  • Tachycardia
  • Insomnia
  • Tremor
  • Anxiety
  • Potential for seizures at extremely high doses

Management: Supportive care focusing on managing hypertension, agitation, and other symptoms; benzodiazepines may help manage agitation and potential seizure risk

Lethal Dose: Not well established in humans; animal studies suggest a very high safety margin with LD50 values many times the therapeutic dose

Case Reports: Published overdose reports are extremely limited; available information suggests significant overdose primarily results in exaggerated stimulant-like effects rather than life-threatening toxicity at typical supratherapeutic exposures

Special Populations

Elderly: Start with lower doses (50-100 mg); increased sensitivity likely due to age-related changes in metabolism and elimination

Hepatic Impairment: Use with caution at reduced doses; approximately 40% undergoes hepatic metabolism

Renal Impairment: Use with caution at reduced doses or avoid in severe impairment; approximately 60% excreted unchanged in urine

Athletes: Banned by World Anti-Doping Agency (WADA) for competitive sports; detected in standard doping tests

Psychiatric Conditions: Use with caution in anxiety disorders; may potentially exacerbate symptoms in some individuals

Quality And Purity Concerns

Common Contaminants: Synthesis byproducts, residual solvents, heavy metals

Testing Recommendations: Third-party testing for identity, purity, and contaminants recommended

Storage Considerations: Store in cool, dry place in airtight container; relatively stable compound but may degrade with exposure to heat, light, or moisture

Harm Reduction Strategies

Harm Reduction Strategies

Start with low doses (50-100 mg) to assess individual sensitivity, Avoid evening dosing to prevent sleep disruption, Consider cycling rather than daily use to minimize tolerance, Combine with adequate choline sources if experiencing headaches, Maintain adequate hydration, Monitor blood pressure if pre-existing cardiovascular concerns, Avoid combination with stimulants or other compounds affecting similar neurotransmitter systems, Purchase from reputable sources with third-party testing, Discontinue use if experiencing significant adverse effects, Consult healthcare provider before use, particularly if taking medications or having medical conditions

Regulatory Status


Global Overview

Phenylpiracetam (Fonturacetam) has a complex and varied regulatory status worldwide. It is an approved pharmaceutical drug in Russia and some Eastern European and Central Asian countries, where it is prescribed for various neurological and cognitive conditions. However, it is not approved as a medication in most Western countries, including the United States, Canada, and the European Union (with possible exceptions in some Eastern European member states). In these regions, it exists in a regulatory gray area, often available as an unregulated supplement or research chemical.

Adding to this complexity, phenylpiracetam is prohibited in competitive sports by the World Anti-Doping Agency (WADA) due to its performance-enhancing properties.

By Country

Russia

  • Approved pharmaceutical drug
  • Russian Ministry of Health
  • Asthenia (weakness/fatigue), cognitive recovery after stroke and traumatic brain injury, cognitive disorders, adaptation to extreme conditions
  • Prescription-only medication
  • Phenotropil, Carphedon, Fonturacetam
  • Has been in clinical use since the 1990s; developed originally for the Soviet space program

Ukraine And Belarus

  • Approved pharmaceutical drug
  • Respective national health ministries
  • Similar to Russia; primarily neurological and cognitive conditions
  • Prescription-only medication
  • Phenotropil and other regional brands
  • Regulatory approach similar to Russia

Kazakhstan And Central Asia

  • Approved pharmaceutical drug in several countries
  • Respective national health ministries
  • Similar to Russia
  • Typically prescription-only
  • Phenotropil and regional variants
  • Regulatory frameworks often follow Russian precedents

United States

  • Not approved as a pharmaceutical drug
  • Food and Drug Administration (FDA)
  • Not scheduled under the Controlled Substances Act
  • Available as an unregulated supplement or research chemical
  • Falls into a gray area; not explicitly approved as a dietary supplement ingredient under DSHEA, but not specifically prohibited
  • FDA could potentially take action against marketing as a dietary supplement, though enforcement has been limited to date

Canada

  • Not approved as a pharmaceutical drug
  • Health Canada
  • Not scheduled under the Controlled Drugs and Substances Act
  • Available as an unregulated supplement or research chemical
  • Not approved as a Natural Health Product (NHP)
  • Exists in regulatory gray area similar to the United States

European Union

  • Not centrally approved as a pharmaceutical drug by the European Medicines Agency (EMA)
  • EMA and national regulatory bodies
  • May have different status in some Eastern European member states where it was previously approved before EU accession
  • Available as an unregulated supplement or research chemical in many EU countries
  • Not listed in the Novel Food Catalogue; regulatory approach varies by member state
  • Complex regulatory landscape with significant variation between member states

United Kingdom

  • Not approved as a pharmaceutical drug
  • Medicines and Healthcare products Regulatory Agency (MHRA)
  • Not controlled under the Misuse of Drugs Act
  • Available as an unregulated supplement or research chemical
  • Potentially subject to the Psychoactive Substances Act 2016, though enforcement regarding phenylpiracetam has been limited
  • Post-Brexit regulatory environment continues to evolve

Australia

  • Not approved as a pharmaceutical drug
  • Therapeutic Goods Administration (TGA)
  • Not listed in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP)
  • Regulatory status as a supplement is complex; may be restricted under various provisions
  • Australia generally takes a more restrictive approach to unapproved substances compared to the US and EU
  • Importation for personal use may be possible under specific conditions, though this exists in a gray area

Japan

  • Not approved as a pharmaceutical drug
  • Pharmaceuticals and Medical Devices Agency (PMDA)
  • Limited; not commonly available as a supplement
  • Japan has strict regulations regarding unapproved pharmaceutical-like substances
  • Not widely used or recognized in Japanese markets

Sports Regulation

Wada Status: Prohibited substance in-competition and out-of-competition

Classification: Listed under S6 (Stimulants) of the WADA Prohibited List

Year Added: 2006

Testing: Detectable in standard doping tests; typically screened for in urine samples

Penalties: Positive tests may result in competition bans ranging from months to years, depending on circumstances

Notes: Athletes subject to doping controls should avoid phenylpiracetam completely

Import Export Regulations

Personal Importation

  • Personal importation of unapproved drugs is technically not permitted under FDA regulations, though enforcement for small quantities for personal use is variable
  • Varies by member state; generally allowed in small quantities for personal use in many countries
  • Small quantities for personal use typically permitted, though subject to change
  • May be permitted under the Personal Importation Scheme with restrictions
  • Small quantities for personal use (typically 90-day supply) generally permitted
  • Regulations can change and enforcement varies; travelers should research current rules before attempting to cross borders with phenylpiracetam

Commercial Importation

  • Limited to countries where approved as a medication
  • Complex regulatory landscape; importers should seek legal guidance specific to their jurisdiction
  • May be imported for research purposes with appropriate documentation in some jurisdictions
  • Commercial importation generally faces more stringent enforcement than personal importation

Labeling And Marketing Regulations

Pharmaceutical Markets

  • Must comply with pharmaceutical labeling regulations in countries where approved as a medication
  • Can make specific medical claims for approved indications in countries where registered as a pharmaceutical

Supplement Markets

  • Cannot make disease treatment claims; structure/function claims must include FDA disclaimer
  • Cannot make medicinal claims; health claims require EFSA approval (none currently exist for phenylpiracetam)
  • Marketing as a dietary supplement in regions where not approved as such may attract regulatory scrutiny

Research Chemical Markets

  • Usually labeled ‘not for human consumption’ or ‘for research purposes only’
  • This labeling approach exists in a legal gray area and may not provide protection against regulatory action

Enforcement Trends

United States

  • Limited specific enforcement actions targeting phenylpiracetam to date
  • Occasional seizures of shipments, though inconsistent
  • Generally low enforcement priority compared to more concerning substances, though this could change

European Union

  • Enforcement varies significantly between member states
  • Generally limited enforcement regarding personal use quantities

Sports Authorities

  • High; regular testing for phenylpiracetam in competitive athletes
  • Significant penalties for positive tests, including competition bans

Regulatory Challenges

Classification Difficulties

  • Phenylpiracetam has pharmaceutical properties and uses in some countries but is marketed as a supplement in others
  • Not traditionally used as a food or supplement ingredient before modern regulatory frameworks were established
  • Sports prohibition creates additional regulatory complexity

International Harmonization

  • Significant differences in regulatory approach between Eastern European countries (where approved as a medication) and Western countries
  • Language barriers in research literature complicate regulatory assessment
  • Regulatory approaches to cognitive enhancers continue to develop globally

Future Outlook

Potential Developments

  • Increased Western research interest may eventually lead to reconsideration of regulatory status in some countries
  • Potential for greater international regulatory harmonization, though significant barriers exist
  • Development of new phenylpiracetam derivatives or formulations may create new regulatory questions

Regulatory Trends

  • Growing regulatory attention to cognitive enhancement substances generally
  • Likely continued prohibition in competitive sports
  • Potential for increased scrutiny of gray-area nootropics in supplement markets

Compliance Recommendations

For Individuals

  • Research current regulations in your jurisdiction before purchasing or using phenylpiracetam
  • Avoid traveling internationally with phenylpiracetam without researching destination country regulations
  • Athletes subject to doping controls should avoid completely
  • Consider medical supervision when possible, particularly for therapeutic applications

For Businesses

  • Avoid making disease claims or explicit medical claims in regions where not approved as a pharmaceutical
  • Seek legal guidance before importing for commercial purposes
  • Implement rigorous testing and quality control regardless of regulatory requirements
  • Provide clear information about regulatory status to customers

Historical Regulatory Changes

Pharmaceutical Approval

  • First approved in Russia in the 1990s following development in the Soviet space program
  • Approval expanded to other post-Soviet states in subsequent years

Sports Regulation

  • Added to the WADA Prohibited List in 2006 after recognition of significant performance-enhancing effects
  • Testing protocols developed and implemented in international sports competitions

Supplement Market Emergence

  • Began appearing in Western supplement and nootropic markets in the 2000s
  • Variable regulatory approaches developed across different jurisdictions

Last Updated

2024-11-20

Disclaimer

Regulatory status is subject to change. This information is provided for educational purposes only and should not be relied upon for legal compliance. Individuals and companies should consult current regulations in their jurisdiction and seek professional legal advice for specific compliance questions.

Synergistic Compounds


Compound: Alpha-GPC (L-Alpha glycerylphosphorylcholine)
Synergy Mechanism: Alpha-GPC provides choline, a precursor to acetylcholine, which complements phenylpiracetam’s effects on cholinergic neurotransmission. Phenylpiracetam may increase acetylcholine utilization and receptor sensitivity, while Alpha-GPC ensures adequate substrate availability for acetylcholine synthesis, creating a synergistic enhancement of cognitive function.
Evidence Rating: 3
Recommended Dosage: 300-600 mg Alpha-GPC taken simultaneously with phenylpiracetam
Safety Considerations: Generally well-tolerated combination. Some individuals may experience headaches, gastrointestinal discomfort, or increased cholinergic effects (sweating, salivation). Start with lower doses of both compounds when combining.
Research Notes: While specific studies on this combination are limited, the synergy is well-established based on their complementary mechanisms. Many users report enhanced cognitive effects and reduced incidence of headaches (a common side effect attributed to acetylcholine depletion) when combining phenylpiracetam with Alpha-GPC.

Compound: CDP-Choline (Citicoline)
Synergy Mechanism: Similar to Alpha-GPC, CDP-Choline provides choline for acetylcholine synthesis, supporting phenylpiracetam’s cholinergic effects. Additionally, CDP-Choline provides cytidine, which converts to uridine and supports neuronal membrane synthesis and dopaminergic function, potentially enhancing phenylpiracetam’s effects on dopamine systems.
Evidence Rating: 3
Recommended Dosage: 250-500 mg CDP-Choline taken simultaneously with phenylpiracetam
Safety Considerations: Generally well-tolerated combination with minimal adverse effects. Similar precautions as with Alpha-GPC.
Research Notes: CDP-Choline has more research supporting its independent neuroprotective effects compared to Alpha-GPC, potentially making this combination particularly beneficial for cognitive protection and recovery applications.

Compound: L-Theanine
Synergy Mechanism: L-Theanine promotes alpha brain wave activity and has calming effects without sedation, which can balance phenylpiracetam’s stimulatory properties. This combination may provide enhanced focus and cognitive function while reducing potential anxiety or jitteriness from phenylpiracetam.
Evidence Rating: 2
Recommended Dosage: 100-200 mg L-Theanine taken simultaneously with phenylpiracetam
Safety Considerations: Very safe combination with minimal risk of adverse effects. May be particularly beneficial for individuals sensitive to stimulation or prone to anxiety.
Research Notes: While specific studies on this combination are lacking, the complementary pharmacological profiles and extensive anecdotal reports support the synergy. L-Theanine is well-studied for its ability to moderate the effects of stimulants without reducing their cognitive benefits.

Compound: Bacopa Monnieri
Synergy Mechanism: Bacopa enhances memory formation through different mechanisms than phenylpiracetam, including antioxidant effects, acetylcholinesterase inhibition, and enhancement of dendritic branching. When combined with phenylpiracetam’s effects on neurotransmitter systems and receptor modulation, this may provide complementary cognitive enhancement.
Evidence Rating: 2
Recommended Dosage: 300-600 mg of standardized Bacopa extract (50% bacosides) daily, not necessarily timed with phenylpiracetam dosing
Safety Considerations: Generally safe combination. Bacopa requires consistent daily use for optimal effects, while phenylpiracetam is often used cyclically to prevent tolerance. Consider this difference in usage patterns when combining.
Research Notes: The combination leverages different mechanisms and timeframes of action: phenylpiracetam provides acute cognitive enhancement while Bacopa offers cumulative benefits with regular use over weeks to months.

Compound: Rhodiola Rosea
Synergy Mechanism: Rhodiola’s adaptogenic properties complement phenylpiracetam’s cognitive effects by reducing mental fatigue, supporting stress resilience, and modulating neurotransmitter activity. Rhodiola may also help mitigate potential tolerance to phenylpiracetam’s stimulatory effects.
Evidence Rating: 2
Recommended Dosage: 200-400 mg of standardized Rhodiola extract (3% rosavins, 1% salidroside) taken in the morning with phenylpiracetam
Safety Considerations: Generally well-tolerated combination. Both compounds have mild stimulatory effects, so monitor for excessive stimulation, especially in sensitive individuals.
Research Notes: Both compounds have been studied for their effects on physical and mental performance under stress or fatigue, suggesting particular synergy for cognitive enhancement in challenging conditions.

Compound: Noopept (N-phenylacetyl-L-prolylglycine ethyl ester)
Synergy Mechanism: Noopept and phenylpiracetam affect overlapping but distinct aspects of glutamatergic, cholinergic, and neurotrophic systems. Noopept’s effects on BDNF and NGF expression may complement phenylpiracetam’s neurotransmitter modulation for enhanced cognitive function and neuroprotection.
Evidence Rating: 2
Recommended Dosage: 10-30 mg Noopept taken simultaneously with phenylpiracetam
Safety Considerations: Use with caution; both compounds are potent cognitive enhancers with stimulatory properties. Start with lower doses of each when combining (e.g., 50-100 mg phenylpiracetam and 10 mg Noopept). Monitor for excessive stimulation or anxiety.
Research Notes: Limited specific research on this combination, though both compounds have been well-studied individually in Russian scientific literature. The combination is popular in advanced nootropic communities, with users reporting enhanced and broader cognitive effects compared to either compound alone.

Compound: Uridine Monophosphate
Synergy Mechanism: Uridine supports neuronal membrane synthesis, synaptogenesis, and dopaminergic function, which may complement phenylpiracetam’s effects on neurotransmitter systems and receptor function. This combination may enhance both acute cognitive effects and long-term neuroplasticity.
Evidence Rating: 1
Recommended Dosage: 250-500 mg Uridine Monophosphate daily, not necessarily timed with phenylpiracetam dosing
Safety Considerations: Generally safe combination with minimal risk of adverse interactions. Uridine is typically taken consistently for cumulative benefits, while phenylpiracetam is often used cyclically.
Research Notes: Limited specific research on this combination, but the complementary mechanisms suggest potential synergy, particularly for long-term cognitive enhancement when uridine is taken consistently alongside cycled phenylpiracetam.

Compound: Fish Oil (EPA/DHA)
Synergy Mechanism: Omega-3 fatty acids support neuronal membrane fluidity, neurotransmitter receptor function, and anti-inflammatory processes in the brain, which may enhance phenylpiracetam’s effects on synaptic plasticity and neurotransmission. DHA is particularly important for maintaining optimal neuronal membrane composition.
Evidence Rating: 2
Recommended Dosage: 1-2 g combined EPA/DHA daily, not necessarily timed with phenylpiracetam dosing
Safety Considerations: Very safe combination with minimal risk of adverse interactions. Fish oil is typically taken consistently for cumulative benefits.
Research Notes: While specific studies on this combination are lacking, omega-3 supplementation has been shown to enhance the efficacy of various cognitive interventions, suggesting potential benefit when combined with phenylpiracetam.

Antagonistic Compounds


Compound: GABAergic compounds (Phenibut, Benzodiazepines, Alcohol)
Interaction Type: Functional antagonism
Mechanism: GABAergic compounds produce inhibitory effects in the central nervous system that may counteract phenylpiracetam’s stimulatory and cognitive-enhancing properties. While not directly interacting at the receptor level, their opposing functional effects on neuronal excitability and neurotransmitter systems may reduce the benefits of each compound.
Evidence Rating: 2
Clinical Significance: Moderate
Management Strategy: Avoid combining unless specifically intended to moderate phenylpiracetam’s stimulatory effects. If combination is necessary, separate dosing by several hours. For alcohol specifically, consider skipping phenylpiracetam on days when alcohol consumption is planned.
Research Notes: Limited specific research, but pharmacological principles and anecdotal reports suggest diminished cognitive benefits when combined. Some users report that phenylpiracetam may mask the subjective feeling of intoxication from alcohol without reducing actual impairment, potentially leading to unsafe alcohol consumption.

Compound: Anticholinergic medications
Interaction Type: Pharmacological antagonism
Mechanism: Anticholinergic drugs block acetylcholine receptors or reduce acetylcholine availability, potentially counteracting phenylpiracetam’s cholinergic-enhancing effects and reducing cognitive benefits. Phenylpiracetam appears to enhance cholinergic neurotransmission, which would be directly opposed by anticholinergic compounds.
Evidence Rating: 2
Clinical Significance: Moderate to high
Management Strategy: Avoid combining when possible. If anticholinergic medication is necessary (e.g., for medical conditions), be aware that phenylpiracetam may not provide optimal cognitive benefits. Consider alternative nootropics with different mechanisms if anticholinergic medications cannot be avoided.
Research Notes: Based on established pharmacological principles rather than specific studies on the combination. Common anticholinergic medications include certain antihistamines (diphenhydramine), some antipsychotics, tricyclic antidepressants, and medications for overactive bladder.

Compound: Dopamine antagonists (Antipsychotics)
Interaction Type: Pharmacological antagonism
Mechanism: Dopamine antagonists block dopamine receptors, directly opposing one of phenylpiracetam’s key mechanisms of action. Phenylpiracetam appears to enhance dopaminergic neurotransmission through reuptake inhibition and possibly other mechanisms, which would be counteracted by dopamine receptor blockade.
Evidence Rating: 2
Clinical Significance: High
Management Strategy: Avoid combination. If antipsychotic medication is necessary, phenylpiracetam is unlikely to provide significant benefits and may potentially interfere with the therapeutic effects of the antipsychotic.
Research Notes: Based on pharmacological principles; specific studies on the interaction are lacking. Relevant medications include typical and atypical antipsychotics used for schizophrenia, bipolar disorder, and other psychiatric conditions.

Compound: Certain antihypertensive medications
Interaction Type: Pharmacological and functional antagonism
Mechanism: Phenylpiracetam may increase blood pressure through sympathomimetic effects, potentially counteracting the effects of antihypertensive medications. Additionally, certain antihypertensives that act on central adrenergic systems may directly oppose phenylpiracetam’s noradrenergic effects.
Evidence Rating: 2
Clinical Significance: Moderate
Management Strategy: Monitor blood pressure if combining. Consult healthcare provider about potential interactions with specific antihypertensive medications. Central-acting agents like clonidine may have more significant antagonistic effects than peripheral-acting agents.
Research Notes: Limited specific research, but based on phenylpiracetam’s known effects on sympathetic nervous system activation. The interaction may be bidirectional, with phenylpiracetam potentially reducing antihypertensive efficacy and certain antihypertensives potentially reducing phenylpiracetam’s cognitive effects.

Compound: Adenosine agonists
Interaction Type: Functional antagonism
Mechanism: Adenosine agonists promote sleep and sedation, effects that would oppose phenylpiracetam’s wakefulness-promoting and cognitive-enhancing properties. While the direct interaction with adenosine systems is not a primary mechanism of phenylpiracetam, the functional opposition could reduce benefits.
Evidence Rating: 1
Clinical Significance: Low to moderate
Management Strategy: Avoid combining unless specifically intended to moderate phenylpiracetam’s effects. Relevant adenosine agonists include medications like adenosine (used for cardiac procedures) and natural compounds that enhance adenosine signaling.
Research Notes: Theoretical interaction based on opposing functional effects; limited specific research available.

Compound: NMDA antagonists (Ketamine, Memantine, DXM)
Interaction Type: Potential pharmacological antagonism
Mechanism: Phenylpiracetam may enhance glutamatergic neurotransmission and NMDA receptor function as part of its cognitive-enhancing effects, while NMDA antagonists block these receptors. This opposition could potentially reduce the cognitive benefits of phenylpiracetam.
Evidence Rating: 1
Clinical Significance: Unknown; potentially moderate
Management Strategy: Approach combination with caution. If NMDA antagonists are used therapeutically (e.g., memantine for Alzheimer’s disease), be aware that phenylpiracetam’s effects may be altered.
Research Notes: Largely theoretical based on presumed mechanisms; specific studies on the interaction are lacking. The complex effects of both classes of compounds on various aspects of glutamatergic signaling make the net interaction difficult to predict.

Cost Efficiency


Cost Overview

Summary: Phenylpiracetam is moderately expensive compared to many other nootropics and cognitive enhancers, but its high potency means that effective doses are relatively small (100-200 mg), improving its cost-efficiency. The need for cycling to prevent tolerance development also reduces the total amount consumed over time compared to daily-use supplements. When comparing cost-effectiveness, it’s important to consider not just the price per gram but the price per effective dose and the quality of effects for specific applications.

Price Ranges: Price Per Gram: $2-5 USD per gram when purchased in quantities of 5-25 grams, Price Per Dose: $0.20-1.00 USD per dose (100-200 mg), Notes: Most cost-effective form for regular users comfortable with measuring powder, Price Per Bottle: $25-45 USD for 30-60 capsules (typically 100-150 mg each), Price Per Dose: $0.75-1.50 USD per dose, Notes: Convenience premium of 50-100% compared to bulk powder, Price In Russia: Approximately $15-30 USD for 30 tablets (100 mg) of Phenotropil, Price Per Dose: $0.50-1.00 USD per dose in pharmaceutical markets, Notes: Not legally available in many Western markets; prices reflect Russian pharmaceutical market

Regional Variations: Significantly lower prices for pharmaceutical-grade products where approved as medication, Higher prices for supplement-grade products; primarily available through specialty nootropic vendors, Moderate prices; availability and pricing vary significantly by country, Limited availability in most markets; pricing typically higher than Western markets when available

Comparative Value

Vs Other Racetams

  • Approximately 30-60 times more potent than piracetam, requiring much smaller doses. While phenylpiracetam costs 10-15 times more per gram than piracetam, the higher potency makes it more cost-effective on a per-dose basis for many applications.
  • Similar cost per effective dose, but phenylpiracetam typically provides stronger effects, particularly for focus and physical performance. Aniracetam may offer better value for anxiety reduction.
  • Phenylpiracetam is approximately 2-3 times more expensive per gram but 5-10 times more potent, making it potentially more cost-effective for many users.
  • Phenylpiracetam’s additional effects on dopamine and norepinephrine systems provide benefits not found with other racetams, potentially justifying the higher cost for specific applications.

Vs Other Nootropics

  • Pharmaceutical modafinil costs $5-15 per dose; generic modafinil $1-3 per dose; phenylpiracetam $0.50-1.50 per dose. Modafinil provides longer duration (8-12 hours vs. 4-6 hours) but phenylpiracetam may offer better value for shorter tasks requiring intense focus.
  • Similar cost per effective dose, but phenylpiracetam avoids the liver concerns associated with adrafinil’s metabolism.
  • Both are highly potent and cost-effective. Noopept is slightly less expensive per dose but has a different effect profile. Value comparison depends on specific desired effects.
  • Effect profiles differ significantly between these alternatives; cost comparison should consider desired outcomes and individual response.

Vs Conventional Stimulants

  • Significantly more expensive than caffeine on a per-dose basis, but offers different and often more comprehensive cognitive enhancement without the same side effect profile.
  • Much less expensive than prescription stimulants without insurance coverage; comparable to generic medications with insurance for some individuals.
  • Phenylpiracetam offers a different risk-benefit profile than conventional stimulants, with potentially fewer side effects for many users.

Value Considerations

Effectiveness Factors

  • Significant differences in response between individuals affect personal value assessment. Some users report dramatic benefits worth the cost, while others experience minimal effects.
  • Value is highly dependent on appropriate cycling to prevent tolerance. Daily use typically leads to diminishing returns within 1-2 weeks.
  • Value varies by application; particularly cost-effective for occasional high-performance demands rather than daily cognitive support.

Quality Factors

  • Higher-purity products typically command 20-30% price premiums but may offer more consistent effects and reduced side effects.
  • Pharmaceutical-grade products from countries where phenylpiracetam is an approved medication may offer better quality assurance, though at similar or sometimes lower prices than Western supplement versions.
  • Products with third-party testing verification typically cost 15-25% more than untested alternatives.

Hidden Costs

  • Accurate scale ($20-50 USD) required for bulk powder use.
  • Potential need for choline supplements ($10-30 monthly) to prevent headaches and optimize effects.
  • Alternative supplements for off-cycle periods may add to total cognitive enhancement budget.

Cost Optimization Strategies

Purchasing Strategies

  • Buying larger quantities of powder can reduce per-dose cost by 30-50%, though increases upfront investment.
  • In countries where legal, pharmaceutical-grade products may offer better value than supplement versions.
  • Some vendors offer 10-15% discounts for subscription purchases.
  • Many supplement retailers offer significant discounts (20-40%) during major sales events.

Usage Optimization

  • Starting with lower doses (50-100 mg) and titrating up only if needed can significantly reduce costs.
  • Using only for high-value cognitive tasks rather than daily can optimize cost-benefit ratio.
  • Implementing proper cycling protocols (e.g., 2 weeks on, 1 week off) prevents tolerance development and reduces total consumption.
  • Combining with complementary compounds like Alpha-GPC or L-Theanine may enhance effects at lower doses.

Alternative Approaches

  • Using phenylpiracetam for high-priority tasks and less expensive alternatives for routine cognitive support.
  • Alternating between phenylpiracetam and other cognitive enhancers to prevent tolerance while maintaining benefits.
  • Combining with free or low-cost cognitive enhancement strategies like exercise, sleep optimization, and meditation.

Market Factors

Supply Chain

  • Primarily manufactured in Russia, China, and some Eastern European countries.
  • Import regulations and shipping costs contribute significantly to Western market pricing.
  • Relatively limited number of manufacturers leads to less price competition than more commoditized supplements.

Market Segmentation

  • Regulated pharmaceutical products in countries where approved as medication; consistent quality at moderate prices.
  • High-quality, third-party tested products from established nootropic vendors; highest pricing in Western markets.
  • Lower-cost options with less quality assurance; significant quality risk but potential value for informed consumers.
  • Variable quality and pricing; marketed for research rather than consumption.

Pricing Trends

  • Relatively stable pricing over the past decade with gradual decreases as production has scaled.
  • Some price increases (10-20%) in 2020-2022 due to global supply chain disruptions.
  • Likely continued stability with potential modest decreases as production efficiency improves and competition increases.

Value Maximization Recommendations

For Occasional Users

  • Purchase smaller quantities of capsules from reputable vendors for convenience and precise dosing.
  • $15-30 USD for twice-weekly use.
  • Use strategically for high-value cognitive tasks rather than routine enhancement.

For Regular Users

  • Purchase bulk powder from established vendors with quality testing.
  • $20-40 USD for cycled use (e.g., 2 weeks on, 1 week off).
  • Invest in accurate scale; implement proper cycling protocol; combine with complementary supplements.

For Specific Applications

  • Most cost-effective when used for specific high-demand cognitive tasks rather than daily enhancement.
  • Valuable for occasional intense training sessions; prohibited for competitive athletes subject to WADA testing.
  • May offer significant value for cognitive support during recovery from injury or illness, though medical supervision is recommended for these applications.

Consumer Guidance

Identifying Value

  • Clear disclosure of exact phenylpiracetam content; specific information about form (powder, capsules); accessible testing documentation.
  • Unusually low pricing; lack of specific product information; excessive marketing claims; absence of quality testing information.
  • Third-party testing verification; clear manufacturer information; professional packaging with proper labeling.

Cost Benefit Analysis

  • Maintain personal log of effects to determine individual value proposition.
  • Test different protocols and formulations to identify optimal personal approach.
  • Factor in cycling requirements and potential need for complementary supplements when assessing long-term value.

Ethical Considerations

  • Consider legal status in your jurisdiction when assessing value and making purchasing decisions.
  • Athletes subject to doping controls should avoid phenylpiracetam regardless of perceived value.
  • Support companies with transparent sourcing, quality testing, and responsible marketing practices.

Last Updated

2024-11-20

Disclaimer

Cost information is approximate and subject to market fluctuations. Individual experiences with phenylpiracetam vary significantly, affecting personal value assessment. This analysis does not constitute an endorsement of phenylpiracetam use, which carries certain risks and should be approached with appropriate caution and research.

Stability Information


Shelf Life

Pharmaceutical Grade: 2-3 years when properly stored in original sealed container under recommended conditions

Supplement Grade: 1-3 years depending on manufacturing quality, packaging, and storage conditions

Research Grade: 2-3 years for high-purity material properly stored

Opened Containers: Recommended use within 1-2 years after opening, with proper resealing and storage

Storage Recommendations

Temperature

  • 15-25°C (59-77°F)
  • 5-30°C (41-86°F)
  • Brief exposure to temperatures outside the acceptable range is unlikely to cause significant degradation, but repeated or prolonged temperature cycling can accelerate degradation

Humidity

  • Below 60% relative humidity
  • Phenylpiracetam has moderate hygroscopicity and may absorb moisture from the air, potentially leading to hydrolysis and degradation over time
  • Use of desiccant packets in storage containers; airtight sealing; avoid opening containers in high-humidity environments

Light Exposure

  • Store in opaque or amber containers protected from direct light, particularly sunlight
  • UV and strong visible light may promote oxidation and other degradation reactions, particularly in the presence of oxygen
  • UV spectrum (100-400 nm)

Container Materials

  • Amber glass, opaque high-density polyethylene (HDPE), or similar materials that provide protection from light and moisture
  • Clear containers, low-density polyethylene (LDPE), polyvinyl chloride (PVC)
  • Tight-fitting lids with moisture-resistant seals; child-resistant packaging recommended for safety

Special Considerations

  • For long-term storage of bulk powder, consider vacuum sealing or nitrogen flushing to minimize oxygen exposure
  • When traveling, maintain original packaging when possible or use airtight travel containers; avoid exposure to temperature extremes

Degradation Factors

Factor: Hydrolysis
Impact: Moderate
Mechanism: The amide bond in phenylpiracetam can undergo hydrolysis in the presence of water, particularly at elevated temperatures or extreme pH conditions
Indicators: Reduced potency; potential formation of phenylacetic acid derivatives with characteristic odor
Prevention: Store in dry conditions with desiccant; use airtight containers; avoid exposure to extreme pH conditions

Factor: Oxidation
Impact: Low to moderate
Mechanism: Oxidative processes may affect the pyrrolidone ring or phenyl group, particularly in the presence of light, heat, or catalytic impurities
Indicators: Slight discoloration (yellowing); reduced potency
Prevention: Minimize oxygen exposure; protect from light; avoid storage with oxidizing agents

Factor: Heat
Impact: Moderate
Mechanism: Elevated temperatures accelerate most degradation reactions, including hydrolysis and oxidation
Indicators: Potential discoloration; reduced potency; changes in physical appearance at very high temperatures
Prevention: Store at controlled room temperature; avoid exposure to heat sources, direct sunlight, or hot environments

Factor: Light
Impact: Low to moderate
Mechanism: UV and strong visible light can catalyze degradation reactions, particularly oxidation
Indicators: Slight discoloration; reduced potency over time
Prevention: Store in opaque or amber containers; keep away from direct sunlight and strong artificial light

Factor: Microbial contamination
Impact: Low
Mechanism: Phenylpiracetam itself has limited susceptibility to microbial degradation, but moisture absorption can support microbial growth in the product
Indicators: Visible mold; unusual odor; clumping that doesn’t resolve with gentle agitation
Prevention: Maintain dry storage conditions; use clean, dry utensils when handling

Stability In Different Forms

Powder

  • High when properly stored
  • Maximum surface area for potential degradation but typically packaged with minimal headspace and sometimes with desiccant
  • Exposure to air during handling; potential for moisture absorption if not properly sealed
  • Most common form for bulk purchases; allows flexible dosing

Tablets

  • High
  • Compressed form reduces surface area exposure; often includes stabilizers and protective coatings
  • Manufacturing process may introduce moisture; excipients may affect long-term stability
  • Common form for pharmaceutical-grade products; provides consistent dosing

Capsules

  • High
  • Protected from environmental exposure; convenient dosing
  • Gelatin capsules may be affected by extreme humidity or dryness
  • Common form for supplement-grade products; masks bitter taste

Solutions

  • Low
  • Convenient for precise dosing; no need for weighing
  • Significantly reduced stability; hydrolysis accelerated in aqueous environment
  • Not recommended for long-term storage; best prepared fresh as needed

Stability Testing Methods

Method Application Advantages Limitations
High-Performance Liquid Chromatography (HPLC) Quantitative analysis of phenylpiracetam content and detection of degradation products over time High sensitivity and specificity; can detect small changes in purity Requires specialized equipment and expertise
Fourier-Transform Infrared Spectroscopy (FTIR) Assessment of structural integrity and identification of functional group changes Non-destructive; rapid analysis; can detect structural changes Less sensitive than chromatographic methods for quantitative analysis
Differential Scanning Calorimetry (DSC) Thermal analysis to assess melting point, purity, and potential interactions with excipients Provides information on physical state and potential polymorphism Limited specificity for degradation products
Accelerated stability testing Exposure to elevated temperature and humidity conditions to predict long-term stability Provides stability data in shorter timeframes; helps establish shelf life May not perfectly predict real-world stability under normal conditions
X-Ray Diffraction (XRD) Analysis of crystalline structure and potential polymorphic changes Specific for crystalline structure assessment Limited application for amorphous materials or degradation product identification

Signs Of Degradation

Physical Changes

  • Discoloration (typically slight yellowing)
  • Changes in odor (development of acidic or unusual smell)
  • Clumping or changes in powder flow properties (may indicate moisture absorption)
  • Changes in tablet appearance (spotting, discoloration, or crumbling)

Chemical Indicators

  • Decreased purity as measured by analytical methods
  • Presence of degradation products in chromatographic analysis
  • Changes in melting point (pure phenylpiracetam: approximately 152-156°C)
  • Altered spectroscopic profiles (IR, NMR)

Performance Changes

  • Reduced potency or efficacy
  • Changes in dissolution rate for tablets or capsules
  • Altered taste (typically more bitter or unpleasant)

Stability Enhancing Additives

Pharmaceutical Formulations

Common Additives:
  • Antioxidants (e.g., butylated hydroxytoluene, ascorbic acid)
  • pH stabilizers (buffer systems)
  • Desiccants (silica gel, molecular sieves)
  • Coating agents for tablets (provides moisture and light protection)
Notes: Pharmaceutical-grade products typically include appropriate stabilizers based on stability testing data

Supplement Formulations

Common Additives:
  • Silicon dioxide (as flow agent and moisture control)
  • Magnesium stearate (as lubricant and moisture barrier)
  • Microcrystalline cellulose (as diluent and stabilizer)
Notes: Quality varies widely; better products may include similar stabilizers to pharmaceutical formulations

Compatibility With Common Excipients

Compatible Excipients: Microcrystalline cellulose, Silicon dioxide, Magnesium stearate (in limited quantities), Starch and starch derivatives, Lactose and other common diluents, Gelatin (capsule material)

Potentially Problematic Excipients: Strongly alkaline compounds that might accelerate hydrolysis, Certain oxidizing agents, High concentrations of metal ions that may catalyze degradation

Notes: Compatibility is generally good with most common pharmaceutical excipients used in dry formulations. Liquid formulations present more potential incompatibilities and stability challenges.

Stability During Processing

Milling And Particle Size Reduction

  • Low to moderate
  • Heat generated during processing; increased surface area may accelerate oxidation
  • Use gentle milling techniques; process in controlled environment with low humidity

Compression Into Tablets

  • Low
  • Heat and pressure during compression; interaction with binders and disintegrants
  • Minimize compression force and dwell time; use compatible excipients

Encapsulation

  • Low
  • Exposure to air during processing; potential static electricity issues with fine powders
  • Process in controlled environment with low humidity; minimize processing time

Dissolution In Liquids

  • High
  • Significantly reduced stability in solution; potential for hydrolysis
  • Prepare solutions fresh when possible; use appropriate pH control if longer stability is required

Long Term Storage Recommendations

Optimal Conditions: Store in original container or airtight amber glass container with desiccant at 15-25°C (59-77°F) and <60% relative humidity, protected from light

Monitoring: Periodically check for signs of degradation; consider analytical testing for valuable or large quantities stored long-term

Rotation Strategy: Use oldest stock first; consider implementing a first-in-first-out inventory system

Repackaging Considerations: If repackaging is necessary, minimize exposure to air, moisture, and light; use appropriate containers with desiccant

Disposal Recommendations

Unused or expired phenylpiracetam should be disposed of according to local regulations for pharmaceutical or chemical waste. Do not flush down drains or dispose of in regular household trash. Some communities have medication take-back programs that may accept supplements.

Sourcing


Synthesis Methods

  • Commercial phenylpiracetam is synthesized through chemical modification of piracetam or through direct synthesis from appropriate precursors. The primary industrial synthesis route involves the addition of a phenyl group to the piracetam molecule through various chemical reactions, including phenylation of piracetam or synthesis from phenylacetamide derivatives.
  • In laboratory settings, phenylpiracetam can be synthesized through several routes, including the reaction of phenylacetyl chloride with appropriate amino acid derivatives or through modification of piracetam using phenylation reagents.
  • Synthesis quality can significantly impact the purity, enantiomeric ratio, and safety of the final product. Industrial pharmaceutical production in countries where phenylpiracetam is an approved medication typically follows Good Manufacturing Practices (GMP) with stringent quality control. Unregulated supplement production may have variable quality standards.

Natural Sources

Phenylpiracetam (Fonturacetam) is not found naturally in plants, animals, or food sources. It is a synthetic derivative of piracetam, modified with the addition of a phenyl group to enhance potency and blood-brain barrier penetration.

Commercial Forms

Availability Formulations Quality Standards
Available as a prescription medication in Russia, Ukraine, and some other Eastern European and Central Asian countries. Marketed under brand names including Phenotropil, Carphedon, and Fonturacetam. Typically available as tablets (100 mg) for pharmaceutical use. Subject to pharmaceutical manufacturing regulations in countries where approved as a medication, including purity standards, dosage consistency, and stability testing.
Available as an unregulated supplement in many countries where it is not approved as a pharmaceutical. Commonly sold online through nootropic vendors and specialty supplement retailers. Available as capsules, tablets, and bulk powder. Highly variable; not subject to pharmaceutical regulations in most countries. Quality, purity, and label accuracy depend entirely on the manufacturer and distributor.
Sold by chemical supply companies and specialty vendors for research purposes. Typically available as powder, sometimes in crystalline form. Variable; may range from high-purity analytical grade to lower-quality bulk production.

Regional Availability

  • Available as a prescription medication with established medical uses. Subject to pharmaceutical regulations and quality control. Used clinically for conditions including cognitive impairment after stroke, asthenia (weakness/fatigue), and various organic brain disorders.
  • Not approved as a medication by the FDA. Available as an unregulated supplement or research chemical, primarily through online vendors specializing in nootropics.
  • Not approved as a medication by the EMA (except potentially in some Eastern European member states). Available as an unregulated supplement in many EU countries, though regulatory status varies by country and is subject to change.
  • Not approved as a medication. Regulatory status as a supplement is complex and may be restricted under various provisions.
  • Not approved as a medication. Available as an unregulated supplement, though Health Canada has not specifically evaluated it.
  • Not approved as a medication or recognized dietary supplement ingredient.
  • Banned by the World Anti-Doping Agency (WADA) due to its performance-enhancing properties. Athletes subject to doping controls should avoid phenylpiracetam.

Quality Assessment

Identification Tests:

  • Melting point determination (approximately 152-156°C for pure phenylpiracetam)
  • Infrared (IR) spectroscopy to confirm molecular structure
  • Nuclear Magnetic Resonance (NMR) spectroscopy for structural confirmation
  • Mass spectrometry for molecular weight and fragmentation pattern confirmation
Purity Tests:

  • High-Performance Liquid Chromatography (HPLC) for purity assessment and detection of impurities
  • Gas Chromatography (GC) for volatile impurity detection
  • Elemental analysis for confirmation of elemental composition
  • Chiral chromatography for enantiomeric purity assessment (R vs S form)
Common Contaminants:

  • Synthesis by-products and unreacted precursors
  • Related racetam compounds (piracetam, oxiracetam, etc.)
  • Heavy metals from catalysts or manufacturing equipment
  • Residual solvents from the manufacturing process
Third Party Testing:

Due to the unregulated nature of phenylpiracetam in many markets, third-party testing is highly recommended but not consistently available or performed. Some specialty vendors provide certificates of analysis, though these vary in comprehensiveness and reliability.

Storage And Stability

  • Store in a cool, dry place in an airtight container protected from light. Optimal temperature range is 15-25°C (59-77°F).
  • Pharmaceutical-grade phenylpiracetam typically has a shelf life of 2-3 years when properly stored. Supplement-grade products may claim similar shelf lives, though stability testing may be less rigorous.
  • Exposure to high humidity, extreme temperatures, or strong oxidizing conditions may accelerate degradation. Phenylpiracetam is relatively stable compared to many other supplements but should still be protected from environmental factors.
  • Changes in appearance (discoloration), development of unusual odor, or reduced solubility may indicate degradation.

Purchasing Considerations

Legal Considerations:

Always verify the legal status of phenylpiracetam in your jurisdiction before purchasing. Regulations vary widely by country and are subject to change. While generally not controlled under international drug conventions, it may be regulated under various national provisions, particularly for athletes due to WADA prohibition.

Quality Indicators:

Look for vendors who provide detailed product information, including purity specifications, and ideally third-party testing results. Pharmaceutical products from countries where phenylpiracetam is an approved medication generally have more consistent quality.

Red Flags:

  • Unusually low prices compared to market average
  • Lack of clear information about purity and quality testing
  • Absence of batch testing or quality control information
  • Vendors making explicit medical claims prohibited in their jurisdiction
  • Products with inconsistent effects or unusual side effects
Ethical Considerations:

Consider the ethical implications of purchasing from vendors who may market phenylpiracetam inappropriately or downplay its regulatory status. Support vendors who provide accurate information about both benefits and risks.

Sustainability And Environmental Impact

As a synthetic compound, phenylpiracetam production involves chemical synthesis rather than natural resource extraction. Environmental concerns primarily relate to chemical waste management in manufacturing facilities. Pharmaceutical production in regulated markets typically has waste management protocols, while unregulated production may have variable environmental standards.

Enantiomeric Considerations

  • Commercial phenylpiracetam is typically available as a racemic mixture containing equal amounts of R and S enantiomers. Some research suggests the R-enantiomer (sometimes called carphedon) may have stronger nootropic effects, while the S-enantiomer may contribute more to physical performance enhancement.
  • Single-enantiomer formulations are primarily of research interest and not widely available commercially. Most pharmaceutical and supplement products contain the racemic mixture.
  • Distinguishing between racemic phenylpiracetam and specific enantiomers requires specialized testing methods such as chiral chromatography, which is rarely performed in standard quality control.

Future Sourcing Trends

  • Potential for expanded pharmaceutical approval in additional countries, particularly for specific neurological applications where clinical evidence is strongest.
  • Development of more efficient and environmentally friendly synthesis methods may reduce production costs and environmental impact.
  • Possible future development of single-enantiomer products if research continues to demonstrate differential effects of R and S forms.
  • Likely continued evolution of regulatory approaches as more research emerges on efficacy and safety profiles.

Historical Usage


Discovery And Development

Discovery: Phenylpiracetam (Fonturacetam) was first synthesized in 1983 at the Institute of Biomedical Problems in Moscow, Russia. It was developed as part of the Soviet space program’s efforts to create medications that could help cosmonauts maintain cognitive function and physical performance under the extreme stresses of space flight.

Initial Research: Early research focused on phenylpiracetam’s ability to enhance physical and mental performance under stressful conditions, particularly in cold environments. It was found to be significantly more potent than its parent compound piracetam, requiring much lower doses for comparable or superior effects.

Space Program Connection: Phenylpiracetam was included in the medical kit of Soviet cosmonauts and was used during space missions to help maintain cognitive function, combat fatigue, and enhance adaptation to the stresses of space flight. This application gave it the nickname ‘the cosmonaut drug’ in some circles.

Medical Use Timeline

1980s: Initial development and testing in the Soviet Union. Early clinical applications for various neurological conditions began to emerge toward the end of the decade.

1990s: Expanded clinical use in Russia and some Eastern European countries. Registered as a pharmaceutical in Russia under the brand name Phenotropil. Research continued on various applications, including stroke recovery, traumatic brain injury, and cognitive disorders.

2000s: Further clinical research and expanded medical applications in Russia and neighboring countries. Began to gain attention in Western countries as a nootropic supplement, though not approved as a medication outside Eastern Europe.

2010s: Continued medical use in Russia and some Eastern European countries. Growing popularity as a cognitive enhancer and performance-enhancing supplement worldwide, despite lack of regulatory approval in Western countries. Added to the World Anti-Doping Agency (WADA) Prohibited List in 2006 due to its performance-enhancing properties.

Traditional Medical Applications

Neurological Recovery: One of the primary approved indications in countries where phenylpiracetam is a registered medication. Used for cognitive and functional recovery after stroke, traumatic brain injury, and other cerebrovascular events.

Asthenia: Widely prescribed for asthenia (weakness and fatigue), particularly in post-infectious, post-traumatic, or neurological contexts. Valued for its ability to combat fatigue without the significant side effects of traditional stimulants.

Cognitive Disorders: Used in the treatment of various cognitive disorders, including age-related cognitive decline, organic brain syndrome, and cognitive impairment associated with cerebrovascular insufficiency.

Adaptation To Extreme Conditions: Employed to enhance adaptation to extreme environmental conditions, particularly cold environments and high altitudes. This application stemmed from its original development for the space program.

Epilepsy Adjunct: In some cases, used as an adjunctive treatment in certain forms of epilepsy, though this is a less common application.

Attention Disorders: Sometimes prescribed for attention deficit disorders, though not as a first-line treatment.

Non Medical Usage Patterns

Cognitive Enhancement: Widely used off-label and as a supplement for cognitive enhancement, particularly for improving focus, attention, memory, and mental energy. Popular among students, professionals, and individuals seeking cognitive benefits.

Physical Performance: Used by athletes and fitness enthusiasts for its performance-enhancing effects, including increased endurance, strength, and recovery. This led to its prohibition by WADA for competitive sports.

Cold Resistance: Used by individuals working in or exposed to cold environments, based on its demonstrated effects on cold tolerance and performance maintenance in low temperatures.

Productivity Enhancement: Adopted by productivity-focused individuals and biohackers seeking to optimize mental performance and work output without the jitteriness or crash associated with traditional stimulants.

Mood Enhancement: Used by some for its mild mood-elevating properties, though this is typically secondary to its cognitive effects.

Cultural Significance

Soviet Space Program: Represents an important development in Soviet space medicine, reflecting the program’s emphasis on pharmacological approaches to human performance optimization in space.

Russian Pharmaceutical Innovation: Stands as an example of significant pharmaceutical development from the Soviet/Russian scientific tradition that has not been widely adopted in Western medicine despite demonstrated efficacy.

Nootropic Movement: Became one of the more potent and respected compounds in the modern nootropics movement, often considered a benchmark against which other cognitive enhancers are compared.

Athletic Performance: Its effectiveness for physical performance enhancement led to its prohibition in sports, highlighting the blurry line between cognitive enhancement and physical performance enhancement.

Regional Variations

Russia And Post Soviet: Recognized pharmaceutical with established medical uses. Prescribed by physicians for approved indications. Available under brand names like Phenotropil and Carphedon.

Western Countries: Not approved as a pharmaceutical. Used as a nootropic supplement or research chemical, primarily by biohackers, nootropics enthusiasts, and individuals seeking cognitive enhancement.

Athletic Community: Prohibited substance for competitive athletes subject to WADA regulations, though potentially still used illicitly in some sports contexts.

Military Applications: Some evidence suggests continued interest in military applications in various countries, particularly for operations in extreme environments, though much of this research is not publicly available.

Historical Research Milestones

Year Development Significance
1983 Initial synthesis at the Institute of Biomedical Problems in Moscow Creation of a significantly more potent derivative of piracetam with enhanced blood-brain barrier penetration
1980s (mid to late) Inclusion in Soviet cosmonaut medical kits Practical application in one of the most demanding human performance environments
1990s (early) Registration as a pharmaceutical in Russia Official medical recognition and expanded clinical applications
2003 Publication of studies demonstrating efficacy in stroke recovery Expanded evidence base for one of its primary clinical applications
2006 Addition to WADA Prohibited List Official recognition of significant performance-enhancing effects in athletics
2010s Growing research on specific mechanisms of action, including AMPA receptor modulation Deeper understanding of pharmacological properties beyond traditional racetam mechanisms

Evolution Of Understanding

Pharmacological Understanding: Initially understood primarily as a more potent version of piracetam with similar mechanisms. Later research revealed more complex pharmacology including dopamine and norepinephrine reuptake inhibition, AMPA receptor modulation, and effects on various other neurotransmitter systems. Recent research has explored the differential effects of its R and S enantiomers.

Therapeutic Potential: Originally developed for performance enhancement in extreme conditions. Applications expanded to include stroke recovery, traumatic brain injury, and various cognitive disorders. Current research continues to explore potential applications in conditions like neurodegenerative disorders and depression.

Risk Assessment: Initially considered to have a very favorable safety profile similar to piracetam. Continued research and widespread use have largely confirmed this assessment, though better understanding of potential for tolerance development and interactions with other substances has emerged.

Lessons From History

Medical Value: Demonstrates the potential value of compounds developed outside the mainstream Western pharmaceutical industry. Highlights how regional differences in medical approaches can lead to valuable but overlooked therapeutic options.

Regulatory Challenges: Illustrates the difficulties in appropriate regulation of cognitive enhancers that exist between established categories of drugs, supplements, and performance enhancers.

Research Gaps: Reveals how language barriers and geopolitical divisions can create significant gaps in scientific knowledge sharing. Much valuable Russian research on phenylpiracetam remained inaccessible to Western scientists for decades.

Enhancement Ethics: Raises important questions about the ethics of cognitive and physical enhancement, particularly in competitive contexts. The prohibition by WADA highlights the challenge of distinguishing between legitimate cognitive support and unfair performance enhancement.

Historical Preparation Methods

Pharmaceutical Formulations

  • The most common pharmaceutical form, typically 100 mg tablets for precise dosing.
  • Some evidence suggests injectable formulations were developed for specific medical applications, though these were not widely used outside of specialized settings.
  • Pharmaceutical preparations typically included appropriate excipients for stability and bioavailability optimization.

Supplement Formulations

  • Common form for supplement market, allowing for convenient dosing without the need for pharmaceutical tableting equipment.
  • Increasingly common in the nootropics community, allowing for flexible dosing but requiring accurate measurement.
  • Quality and consistency of supplement formulations varies significantly compared to pharmaceutical preparations.

Historical Figures And Contributions

Soviet Scientists: The team at the Institute of Biomedical Problems who developed phenylpiracetam deserves primary credit for its creation, though specific individuals are not widely recognized in Western literature.

Cosmonauts: While specific accounts are limited in accessible literature, Soviet/Russian cosmonauts who used phenylpiracetam during space missions provided valuable real-world testing of its effects under extreme conditions.

Clinical Researchers: Russian neurologists and psychiatrists who conducted early clinical studies established the evidence base for its medical applications, though many of these researchers are not widely known outside Russian-language scientific literature.

Future Historical Perspective

Potential Legacy: Phenylpiracetam may eventually be recognized as an important milestone in cognitive enhancement pharmacology, representing a transition from first-generation nootropics like piracetam to more potent and targeted compounds.

Ongoing Evolution: Current research continues to refine understanding of its mechanisms and potential applications, which may lead to development of next-generation derivatives or related compounds.

Ethical Framework Development: The history of phenylpiracetam’s use across medical, enhancement, and athletic contexts may contribute to evolving ethical frameworks for cognitive enhancement in society.

Scientific Evidence


Evidence Rating i

3Evidence Rating: Moderate Evidence – Multiple studies with generally consistent results

Evidence Summary

Phenylpiracetam has a moderate body of scientific evidence supporting its cognitive-enhancing, neuroprotective, and physical performance effects. Most clinical research comes from Russia and Eastern European countries where it is an approved medication (Fonturacetam) for specific conditions. The strongest evidence supports its use for cognitive recovery after cerebrovascular events, asthenia (weakness/fatigue), and cognitive enhancement in organic brain disorders. Evidence for its use in healthy individuals for cognitive enhancement is more limited but mechanistically sound.

Its physical performance-enhancing effects are sufficiently established to warrant its prohibition by the World Anti-Doping Agency (WADA). While the existing research is promising, limitations include relatively small sample sizes in many studies, limited research published in English-language journals, and few large-scale, long-term clinical trials meeting current Western methodological standards.

Key Studies

Study Title: Clinical efficacy of nootropic drug phenotropil in the treatment of stroke patients
Authors: Koval’chuk VV, Skoromets AA, Koval’chuk IV
Publication: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Year: 2008
Doi: Not available
Url: https://pubmed.ncbi.nlm.nih.gov/19008794/
Study Type: Randomized controlled trial
Population: 400 patients recovering from ischemic stroke
Findings: Phenylpiracetam (Phenotropil) treatment led to significant improvements in cognitive function, motor recovery, and activities of daily living compared to standard therapy alone. The treatment group showed better outcomes on multiple standardized scales including the Barthel Index, Rivermead Mobility Index, and Mini-Mental State Examination.
Limitations: Published in Russian with limited English translation; full methodological details not widely accessible in Western scientific literature

Study Title: Efficacy of phenotropil in the rehabilitation of stroke patients
Authors: Gustov AA, Smirnov AA, Korshunova YA, Andrianova YV
Publication: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Year: 2006
Doi: Not available
Url: https://pubmed.ncbi.nlm.nih.gov/16548370/
Study Type: Clinical trial
Population: Stroke patients in rehabilitation
Findings: Phenylpiracetam improved neurological recovery, cognitive function, and reduced asthenia (weakness/fatigue) in stroke patients undergoing rehabilitation. Significant improvements were observed in memory, attention, and executive function.
Limitations: Published in Russian; smaller sample size; limited methodological details available in English

Study Title: Carphedon is a novel nootropic and stimulant drug
Authors: Zvejniece L, Svalbe B, Veinberg G, Grinberga S, Vorona M, Kalvinsh I, Dambrova M
Publication: Behavioral and Brain Functions
Year: 2011
Doi: 10.1186/1744-9081-7-16
Url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118383/
Study Type: Preclinical (animal) study
Population: Rodent models
Findings: Comprehensive investigation of phenylpiracetam’s pharmacological properties, demonstrating its effects on locomotor activity, memory function, and neuroprotection. The study confirmed phenylpiracetam’s ability to enhance physical performance and cognitive function in animal models, with effects on both dopaminergic and central alpha-adrenergic systems.
Limitations: Animal study; may not fully translate to human effects

Study Title: Phenotropil in the treatment of vascular encephalopathy
Authors: Savchenko AY, Zakharova NS, Stepanov IN
Publication: Russian Journal of Clinical Pharmacology and Therapy
Year: 2005
Doi: Not available
Url: Not available online
Study Type: Clinical trial
Population: Patients with chronic cerebrovascular insufficiency
Findings: Phenylpiracetam improved cognitive function, reduced asthenia, and improved quality of life in patients with vascular cognitive impairment. Significant improvements were observed in attention, memory, and executive function after 30 days of treatment.
Limitations: Limited accessibility in English-language literature; methodological details not fully available

Study Title: The nootropic and analgesic effects of phenotropil: possible involvement of the AMPA receptor
Authors: Zvejniece L, Svalbe B, Vavers E, Makrecka-Kuka M, Makarova E, Liepins V, Kalvinsh I, Dambrova M
Publication: European Journal of Pharmacology
Year: 2016
Doi: 10.1016/j.ejphar.2016.05.012
Url: https://pubmed.ncbi.nlm.nih.gov/27178061/
Study Type: Preclinical (animal) study
Population: Rodent models
Findings: Demonstrated that phenylpiracetam’s cognitive-enhancing and pain-relieving effects may involve AMPA receptor modulation. The study provided important insights into the compound’s mechanism of action beyond its previously established effects on monoamine systems.
Limitations: Animal study; focused on specific mechanisms rather than clinical outcomes

Meta Analyses

Title: No comprehensive meta-analyses of phenylpiracetam’s efficacy have been published in peer-reviewed English-language literature
Authors: N/A
Publication: N/A
Year: N/A
Findings: The lack of meta-analyses reflects the limited number of standardized clinical trials available for systematic review, particularly in Western scientific literature

Clinical Applications

Application Evidence Level Key Findings Clinical Use
Post-stroke cognitive recovery Moderate to strong Multiple clinical studies from Russia and Eastern Europe demonstrate improvements in cognitive function, attention, memory, and overall recovery when phenylpiracetam is used as an adjunct therapy in post-stroke rehabilitation. Approved for this indication in Russia and some Eastern European countries; typically used at 100-200 mg daily for 30-60 days
Asthenia (weakness/fatigue) Moderate Clinical studies show reduction in fatigue symptoms and improved energy levels in patients with asthenia of various origins, including post-stroke, neurasthenia, and chronic fatigue. Approved for this indication in some countries; typically used at 100-200 mg daily, often as a morning dose
Cognitive enhancement in organic brain disorders Moderate Studies demonstrate improvements in attention, memory, and executive function in patients with various organic brain disorders, including traumatic brain injury, encephalopathy, and age-related cognitive decline. Used clinically in countries where approved; dosing typically 100-200 mg daily
Cognitive enhancement in healthy individuals Limited but promising Limited formal clinical trials in healthy populations; existing studies and mechanistic understanding suggest benefits for attention, working memory, and mental performance under stress or fatigue. Used off-label and as a supplement; typically 100-200 mg as needed for cognitive demands
Physical performance enhancement Moderate Sufficient evidence for performance-enhancing effects to warrant prohibition by WADA. Studies demonstrate improved endurance, work capacity, and recovery, particularly in cold environments. Prohibited in competitive sports; used by some athletes in training at 100-200 mg pre-workout
Cold tolerance Moderate Research from Russia demonstrates improved performance and adaptation to cold environments, originally studied for potential use by military personnel and cosmonauts. Used in specific occupational contexts requiring cold exposure; typically 100-200 mg prior to cold exposure

Mechanisms Of Action Evidence

Neurotransmitter Effects

  • Strong
  • Well-established effects on multiple neurotransmitter systems, including dopamine, norepinephrine, acetylcholine, and glutamate. Acts as a dopamine and norepinephrine reuptake inhibitor, enhances acetylcholine release, and modulates AMPA and NMDA glutamate receptors.

Neuroprotective Effects

  • Moderate
  • Demonstrated neuroprotective properties in models of ischemia, oxidative stress, and neurotoxicity. Mechanisms include antioxidant effects, improved cerebral blood flow, enhanced glucose utilization, and modulation of neuronal excitability.

Physical Performance Mechanisms

  • Moderate
  • Effects on physical performance linked to central nervous system stimulation via dopaminergic and adrenergic mechanisms, rather than direct effects on muscle tissue. May enhance motivation, reduce perception of fatigue, and improve central motor control.

Pharmacological Evidence

Receptor Binding

  • Moderate
  • Studies demonstrate binding to dopamine transporters, nicotinic acetylcholine receptors, and modulation of glutamate receptor function. The R-enantiomer shows greater affinity for certain receptors than the S-enantiomer.

Electrophysiological Studies

  • Limited
  • Limited but consistent evidence showing effects on neuronal excitability, synaptic transmission, and long-term potentiation, supporting its cognitive-enhancing properties.

Blood-brain Barrier Penetration

  • Strong
  • Well-established superior blood-brain barrier penetration compared to piracetam due to the addition of the phenyl ring, resulting in greater lipophilicity and CNS activity at lower doses.

Comparison To Alternatives

Alternative Comparative Findings Evidence Quality
Piracetam Phenylpiracetam is approximately 30-60 times more potent than piracetam, requiring much lower doses for comparable effects. It has greater stimulatory properties, improved blood-brain barrier penetration, and additional effects on dopamine and norepinephrine systems not seen with piracetam. Moderate; several comparative studies available
Modafinil Both compounds enhance wakefulness, attention, and cognitive performance under fatigue. Phenylpiracetam has more pronounced effects on memory and learning, while modafinil may have stronger wakefulness-promoting effects. Phenylpiracetam typically has a shorter duration of action (4-6 hours vs. 8-12 hours for modafinil). Limited; few direct comparison studies
Conventional stimulants (amphetamines) Phenylpiracetam produces milder stimulation with fewer peripheral side effects and lower abuse potential than amphetamines. It enhances cognition through multiple mechanisms beyond catecholamine release, potentially offering more balanced cognitive enhancement. Limited; primarily based on mechanistic comparisons rather than head-to-head studies

Population Specific Evidence

Stroke Patients

  • Moderate to strong
  • Multiple clinical trials demonstrate benefits for cognitive recovery, motor function improvement, and reduction of post-stroke asthenia.

Elderly Individuals

  • Moderate
  • Studies show improvements in age-related cognitive decline, particularly in attention, processing speed, and memory functions.

Healthy Adults

  • Limited
  • Few formal studies in healthy populations; existing evidence suggests benefits for cognitive performance under stress, fatigue, or cognitive demand.

Athletes

  • Moderate
  • Sufficient evidence for performance enhancement to warrant WADA prohibition; studies show improved endurance, work capacity, and cold tolerance.

Ongoing Research

Investigation of phenylpiracetam’s potential applications in neurodegenerative disorders, Research on specific enantiomer effects and potential development of single-enantiomer formulations, Exploration of mechanisms beyond traditional neurotransmitter effects, including AMPA receptor modulation, Studies on optimal dosing regimens to minimize tolerance development, Investigation of potential synergistic combinations with other cognitive enhancers

Research Limitations

Limited number of large-scale clinical trials meeting current Western methodological standards, Much of the research is published in Russian or Eastern European journals with limited accessibility in English, Few long-term safety and efficacy studies beyond 2-3 months of use, Limited research specifically examining effects in healthy individuals for cognitive enhancement, Potential publication bias, with positive results more likely to be published than negative findings, Limited research on optimal dosing, cycling protocols, and tolerance management, Few studies directly comparing phenylpiracetam to other cognitive enhancers or conventional treatments

Expert Consensus

No formal consensus statements from major Western medical organizations regarding phenylpiracetam. In Russia and some Eastern European countries,

it is recognized as an effective nootropic and neuroprotective agent for specific clinical applications. Neuropharmacologists generally acknowledge its cognitive-enhancing and neuroprotective properties based on its pharmacological profile and available clinical evidence, though many emphasize the need for additional well-designed clinical trials to better establish its efficacy and optimal use protocols.

Future Research Directions

Need for well-designed clinical trials meeting international standards, particularly in Western countries, Investigation of long-term safety and efficacy beyond current study durations, Research on optimal cycling protocols to minimize tolerance development, Exploration of potential therapeutic applications in conditions not currently approved, such as ADHD, depression, and neurodegenerative disorders, Development and testing of extended-release formulations to prolong effects, Studies on genetic factors influencing individual response, Research on potential synergistic combinations with other cognitive enhancers or neuroprotective agents

Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.

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