Centrophenoxine

• Cognitive enhancement
• Neuroprotection
• Lipofuscin removal
• Antioxidant activity

• Memory improvement
• Mental alertness
• Neuroplasticity support
• Anti-aging effects
• Mood enhancement

Centrophenoxine operates through multiple mechanisms to exert its cognitive-enhancing and neuroprotective effects. As a DMAE (dimethylaminoethanol) derivative, it serves as a precursor to acetylcholine, a crucial neurotransmitter involved in memory formation, learning, and cognitive processes. Upon administration, Centrophenoxine crosses the blood-brain barrier more effectively than DMAE alone due to its conjugation with p-chlorophenoxyacetic acid (pCPA), which enhances its lipophilicity. Once in the brain, it undergoes hydrolysis to release DMAE, which is then converted to choline and subsequently to acetylcholine, thereby increasing cholinergic neurotransmission.

This enhanced cholinergic activity is believed to underlie many of its cognitive benefits. Beyond its cholinergic effects, Centrophenoxine demonstrates potent antioxidant properties, scavenging free radicals and reducing oxidative stress in neural tissues. It upregulates antioxidant defense systems, including superoxide dismutase (SOD), catalase, and glutathione peroxidase, particularly in aging brains where oxidative damage accumulates. One of Centrophenoxine’s most distinctive properties is its ability to reduce lipofuscin accumulation in neurons.

Lipofuscin, often called the ‘aging pigment,’ consists of oxidized proteins and lipids that accumulate in cells with age and impair cellular function. Studies have shown that Centrophenoxine can decrease lipofuscin deposits by up to 30-40% in aged animal brains, potentially reversing certain aspects of cellular aging. Centrophenoxine also enhances glucose uptake and metabolism in brain cells, improving energy utilization and cellular respiration. This metabolic enhancement is particularly beneficial in aging brains, where glucose metabolism typically declines.

Additionally, it stimulates RNA and protein synthesis in neurons, supporting neuroplasticity and cellular repair mechanisms. Research indicates that Centrophenoxine increases cerebral blood flow and oxygen utilization, potentially improving nutrient delivery to brain tissues. It also modulates membrane fluidity and phospholipid turnover, which may contribute to improved neuronal signaling and communication. Furthermore, Centrophenoxine has been shown to influence various neurotransmitter systems beyond acetylcholine, including norepinephrine and dopamine, which may contribute to its effects on mood and alertness.

Its neuroprotective effects extend to reducing neuroinflammation and inhibiting the formation of advanced glycation end products (AGEs), which are implicated in age-related cognitive decline.

The typical dosage range for Centrophenoxine is 500-2000 mg per day, divided into 1-3 doses. Most studies and clinical applications use 1000-1500 mg daily for optimal effects with minimal side effects.

For optimal absorption and to minimize potential sleep disturbances, Centrophenoxine should be taken earlier in the day, preferably with meals. The last dose should be taken at least 4-6 hours before bedtime to prevent potential sleep disruption due to its stimulating effects. Dividing the daily dosage into 2-3 smaller doses throughout the day may help maintain steady blood levels and reduce the likelihood of side effects.

Some practitioners recommend cycling Centrophenoxine to prevent tolerance and maintain efficacy. A common approach is to take it for 8-12 weeks followed by a 2-4 week break. However, clinical studies on the necessity of cycling are limited, and some individuals may benefit from continuous use, particularly for conditions like age-related cognitive decline.

New users should start with a lower dose (250-500 mg daily) for the first week to assess tolerance, then gradually increase to the target dosage over 2-3 weeks. This approach helps minimize potential side effects and allows for individual dose adjustment based on response.

Centrophenoxine demonstrates relatively high bioavailability compared to DMAE alone, with an estimated oral absorption rate of 70-85%. Its enhanced lipophilicity due to the p-chlorophenoxyacetic acid component facilitates efficient crossing of the blood-brain barrier.

Onset Of Action: 30-60 minutes after oral administration

Peak Plasma Concentration: Achieved within 1-3 hours after ingestion

Half Life: Approximately 3-5 hours in healthy adults

Duration Of Effects: Acute effects typically last 4-6 hours, while cumulative benefits may develop over weeks of consistent use

For optimal absorption and effectiveness, Centrophenoxine is best taken with meals or a small amount of fat. Morning and early afternoon dosing is recommended to prevent potential sleep disturbances, as its stimulating effects may interfere with sleep if taken too late in the day. Dividing the daily dose into 2-3 administrations spaced throughout the day can help maintain more consistent blood levels and cognitive effects.

After absorption, Centrophenoxine is hydrolyzed to release DMAE and p-chlorophenoxyacetic acid. DMAE is primarily metabolized in the liver through various pathways, including conversion to choline and subsequent incorporation into acetylcholine and phospholipids. Metabolites are primarily excreted through the kidneys, with a smaller portion eliminated via bile and feces.

Centrophenoxine has demonstrated a favorable safety profile in both clinical studies and decades of use as a cognitive enhancer. Most adverse effects are mild and transient, particularly when used within recommended dosage ranges. Long-term studies spanning several months have not revealed significant safety concerns, though comprehensive data on multi-year use is limited.

Common:

Uncommon:

Rare:

3000 mg daily is generally considered the maximum safe dose for healthy adults, though most clinical applications use 1000-2000 mg daily. Doses exceeding 3000 mg daily have not been well-studied and may increase the risk of adverse effects without providing additional benefits.

Studies lasting up to 6 months have not identified significant safety concerns with continuous use at recommended dosages. However, comprehensive data on multi-year use is limited. Some practitioners recommend periodic breaks (cycling) to minimize any potential unknown long-term effects and maintain efficacy, though the necessity of this approach is not firmly established by research.

Elderly: Start with lower doses (250-500 mg daily) and titrate gradually; increased sensitivity to both beneficial and adverse effects may occur

Liver Impairment: Consider dose reduction of 25-50%; monitor for prolonged effects due to potentially reduced metabolism

Kidney Impairment: Mild to moderate impairment may require 25% dose reduction; severe impairment has not been adequately studied

Cardiovascular Conditions: Use with caution in individuals with arrhythmias or unstable cardiovascular disease; monitor blood pressure

Acute overdose may present with pronounced cholinergic effects including headache, nausea, vomiting, diarrhea, excessive sweating, hypotension or hypertension, and in severe cases, respiratory depression. No specific antidote exists; treatment is supportive and symptomatic. Reported cases of significant toxicity are rare.

Classification: Dietary Supplement

Approval Status: Not FDA-approved as a drug

Regulatory Framework: Regulated under the Dietary Supplement Health and Education Act (DSHEA) of 1994

Marketing Restrictions: Cannot be marketed with claims to treat, cure, or prevent any disease

Enforcement Actions: No significant FDA enforcement actions specifically targeting Centrophenoxine as of 2024

Notes: While available as a supplement, Centrophenoxine exists in a regulatory gray area. The FDA has not explicitly evaluated its safety or efficacy, but allows its sale under dietary supplement regulations as long as no medical claims are made.

Inclusion In Treatment Protocols: Not included in major clinical guidelines for cognitive disorders in the US or most Western countries

Specialist Recommendations: Some geriatric specialists in Eastern European and Asian countries may include it in protocols for age-related cognitive decline

Research Status: Continues to be studied for potential applications in age-related cognitive conditions, but not considered standard of care

Personal Use: Many countries permit import for personal use in limited quantities, typically 1-3 months supply

Commercial Import: Subject to pharmaceutical or dietary supplement import regulations depending on the country

Customs Considerations: May be subject to detention in countries where not approved; classification may vary between countries

Potential Changes: Increasing scrutiny of cognitive enhancers and nootropics may lead to more defined regulatory frameworks in major markets

Research Impact: Ongoing clinical research may eventually support more formal medical applications in some jurisdictions

Harmonization Efforts: International regulatory harmonization efforts may clarify its status across borders in coming years

Wada Status: Not currently on the World Anti-Doping Agency Prohibited List

Testing: Not typically included in standard anti-doping screening protocols

Sports Organization Policies: No major sports organizations specifically prohibit Centrophenoxine use

Notes: Athletes should exercise caution as regulatory status could change and some sports organizations have broader prohibitions on cognitive enhancers

Medium

Daily Cost Range: $0.30 – $2.00 for typical effective dose (1000-1500 mg)

Monthly Cost Range: $9 – $60 for continuous use

Annual Cost Range: $110 – $720 for continuous use

Notes: Costs vary significantly based on brand, formulation, and purchase volume. Bulk powder forms are typically most economical but require accurate measurement.

Cost Effectiveness Rating: 3.5 out of 5

Cost Vs Benefit Assessment: Centrophenoxine offers moderate to good value for its cognitive enhancement and neuroprotective effects. While not the least expensive nootropic option, its well-established safety profile, multiple mechanisms of action, and decades of research provide reasonable justification for its medium price point. For elderly individuals or those with age-related cognitive concerns, the potential benefits may justify the cost more clearly than for young, healthy individuals seeking purely enhancement effects.

Comparison To Alternatives: Slightly more expensive than plain DMAE supplements, but offers better blood-brain barrier penetration and potentially enhanced effects, justifying the modest price premium, Generally less expensive than Alpha-GPC for cholinergic support, though some users report Alpha-GPC provides stronger acute effects, Substantially more affordable than prescription medications for cognitive enhancement, though effects may be more subtle, Comparable or slightly higher cost than piracetam, but offers different mechanisms of action and potential synergy when combined

Cost Saving Strategies: Purchasing in bulk powder form for those comfortable with accurate measurement, Taking advantage of bulk discounts or subscription options from reputable vendors, Cycling use (e.g., 8 weeks on, 2 weeks off) may extend supply while potentially maintaining benefits, Combining with synergistic compounds may allow for lower effective doses of each

Price Stability: Relatively stable pricing over the past decade with modest inflation-related increases

Availability Trends: Increasing availability through online retailers and specialty supplement stores

Market Competition: Growing number of manufacturers has helped maintain competitive pricing

Future Outlook: Prices likely to remain stable or decrease slightly as manufacturing scale increases and more competitors enter the market

Prescription Status: Not covered by insurance in most countries as it’s typically sold as a supplement rather than a prescription medication

Exceptions: In some European and Eastern European countries where it may be prescribed as a medication (Lucidril), partial coverage may be available under certain healthcare systems

Hsa/fsa Eligibility: Generally not eligible for Health Savings Account or Flexible Spending Account reimbursement in the US unless prescribed by a physician for a specific medical condition

Standard Formulations: 2-3 years when stored properly in original sealed container

Powder Form: 1-2 years when stored in airtight container away from light and moisture

Liposomal Formulations: 6-12 months, often requiring refrigeration after opening

Temperature: Store between 15-25°C (59-77°F). Avoid temperature extremes, as high temperatures can accelerate degradation and freezing may affect physical stability of some formulations.

Humidity: Keep in low-humidity environment. Centrophenoxine can be hygroscopic (absorbs moisture from air), which may lead to degradation or clumping, particularly in powder form.

Light Exposure: Store in opaque or amber containers. Extended exposure to light, especially UV light, may accelerate degradation of the compound.

Container Type: Airtight, opaque containers are ideal. Original packaging typically provides appropriate protection. For bulk powder, consider transferring to small airtight containers with desiccant packets to minimize exposure during regular use.

High-Performance Liquid Chromatography (HPLC) for quantitative analysis of active compound and detection of degradation products, Accelerated stability testing under controlled temperature and humidity conditions to predict long-term stability, Real-time stability testing to confirm shelf-life estimates, pH monitoring to detect hydrolysis-related changes, Appearance evaluation to identify physical changes indicative of degradation

Primary Products: Hydrolysis of Centrophenoxine primarily yields DMAE and para-chlorophenoxyacetic acid (pCPA), the original components used in synthesis

Safety Implications: The primary degradation products are generally considered to have low toxicity. DMAE itself is a supplement, while pCPA has a reasonable safety profile at the concentrations typically present. However, extensive degradation will reduce the efficacy of the product.

Powder Form: If clumping occurs due to moisture exposure, gentle sifting may restore usability. However, if significant degradation is suspected (unusual odor, discoloration, or extensive clumping), the product should be discarded.

Liquid Formulations: If separation occurs in liquid formulations, gentle shaking may restore homogeneity. If crystallization or precipitation is observed, the product may have been exposed to temperature extremes and efficacy could be compromised.

For travel, consider transferring only the needed amount to a small, airtight container rather than exposing the entire supply to variable conditions. Avoid leaving supplements in hot vehicles or checked luggage that may experience temperature extremes. Capsules and tablets generally maintain better stability during travel compared to powders or liquid formulations.

Synthesis Methods

Natural Sources

Quality Considerations

Commercial Forms

Reputable Manufacturers

Storage Recommendations

Centrophenoxine has a rich history spanning over six decades since its development in 1959 by scientists at the French National Scientific Research Center. Originally synthesized as a more effective derivative of DMAE (dimethylaminoethanol), it was designed to enhance brain function and treat age-related cognitive decline. The compound was first marketed under the brand name Lucidril® and was initially used in clinical settings throughout Europe as a prescription medication for senile dementia, Alzheimer’s disease, and other forms of cognitive impairment in the elderly. During the 1960s and 1970s, Centrophenoxine gained significant attention in the scientific community following pioneering research by Dr.

Imre Zs.-Nagy and colleagues, who demonstrated its ability to reduce lipofuscin (cellular aging pigment) accumulation in brain cells. This discovery positioned Centrophenoxine as one of the first potential anti-aging compounds targeting cellular mechanisms of brain aging. Throughout the 1970s and 1980s, clinical use expanded in European countries, particularly in geriatric medicine. Physicians prescribed it for age-associated memory impairment, stroke recovery, and as an adjunctive treatment for dementia.

During this period, it was often used in combination with other nootropics like piracetam in clinical protocols for cognitive enhancement. By the 1990s, with the growing interest in cognitive enhancement and anti-aging interventions, Centrophenoxine began transitioning from purely clinical applications to broader use as a cognitive enhancer among healthy individuals. The emerging nootropics community embraced it as one of the ‘classic’ cognitive enhancers with a long safety record. In the United States, Centrophenoxine never received FDA approval as a pharmaceutical drug but instead entered the market as a dietary supplement following the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA).

This regulatory framework allowed it to be sold without prescription as long as no specific disease claims were made. The early 2000s saw renewed scientific interest in Centrophenoxine’s mechanisms of action, particularly its antioxidant properties and effects on neuronal membrane fluidity. Research during this period helped elucidate its multiple modes of action beyond the original understanding of its cholinergic effects. With the rise of the internet and online communities focused on cognitive enhancement in the 2010s, Centrophenoxine gained popularity among biohackers, students, and professionals seeking cognitive enhancement.

It became a staple in many nootropic ‘stacks’ (combinations of supplements) designed to enhance memory, learning, and overall cognitive function. Today, Centrophenoxine continues to be used both in clinical settings in some countries and as a dietary supplement worldwide. Its long history of use, relatively well-understood mechanism of action, and favorable safety profile have maintained its position as one of the more respected and established nootropic compounds, even as newer cognitive enhancers have entered the market. Current applications span from anti-aging interventions to cognitive enhancement in healthy adults to supportive therapy for various forms of cognitive decline.

Centrophenoxine has a moderate body of scientific evidence supporting its cognitive-enhancing and neuroprotective properties. Research includes a mix of animal studies, limited human clinical trials, and decades of clinical use.

While many studies demonstrate promising results, particularly for age-related cognitive decline and neuroprotection, large-scale, modern randomized controlled trials are somewhat limited. The strongest evidence exists for its effects on lipofuscin reduction, antioxidant activity, and cholinergic enhancement.

Limited large-scale, modern clinical trials in healthy adults, Insufficient data on long-term safety beyond 6-12 months, Limited direct comparisons with other cognitive enhancers, Unclear optimal dosing protocols for different age groups and conditions, Limited research on potential synergistic effects with other nootropics or interventions

Experts generally consider Centrophenoxine to be a moderately effective cognitive enhancer with particular benefits for age-related cognitive decline. Its mechanism as both a cholinergic enhancer and antioxidant is well-established, though opinions vary on its efficacy compared to newer nootropic compounds. Most experts acknowledge its favorable safety profile, particularly compared to prescription cognitive enhancers, while noting the need for additional modern clinical research.

Research on Centrophenoxine began in the late 1950s, with early studies focusing on its potential as a treatment for dementia and age-related cognitive decline. Peak research interest occurred in the 1970s-1980s, with numerous animal studies and limited human trials. Recent decades have seen renewed interest in its mechanisms of action, particularly regarding its antioxidant properties and effects on lipofuscin accumulation, though large-scale human trials remain relatively limited compared to newer pharmaceutical cognitive enhancers.