Phenylpiracetam (Phenotropil, Carphedon, (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide)

PhenylPiracetam (Phenotropil) is a racetam derivative developed in Russia in the 1980’s that acts as both a cognitive enhancer and a psychostimulant. Up until 2006 this nootropic was relatively unknown outside of Russia, however phenylpiracetam gained worldwide attention when Olympic athlete Olga Pyleva was disqualified following a positive drug test.

As the name suggests this molecule is a phenylated derivative of piracetam that is reported to be 20-60 times more potent than piracetam on a gram for gram basis. One study comparing the two reported phenylpiracetam to be more neuroprotective, anti-amnesic and more stimulating that piracetam.

Phenylpiracetam is a racemic mixture of R and S enantiomers. Research suggests the R form to be superior to the S. It’s somewhat a moot point as there is no commercially available source of enantiomerically pure phenylpiracetam.

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Other Names

Phenotropil, Carphedon, (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide

Important Information

Dosing Phenylpiracetam

The manufacturers suggest taking 100mg with food twice per day (1). Anecdotal user reports suggest two doses of 250mg would be classed as a high dose and be potentially too stimulating for some individuals.  The maximum daily dose is set at 750mg by the manufacturers.  User reports suggest insomnia if taken later on, so it is recommend it not be consumed past the late afternoon.

Phenylpiracetam Tolerance

Given the apparent stimulant like nature of this nootropic, it’s probably best taken sporadically on an “as needed” basis, rather than being a staple.  Common sense dictates that tolerance with prolonged use could become an issue, and while there’s been no research conducted on this it’s probably best to cycle phenylpiracetam.

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PhenylPiracetam Absorption

Absorption data for humans remains unpublished. The phenotropil product insert states phenylpiracetam is absorbed fast and exhibits a 100% oral bioavailability. The manufacturer states peak blood concentrations are achieved at 1 hour and the half life for phenylpiracetam is 3-5 hours.

Interestingly the manufacturers insert also states that the drug is not metabolized by the body and thus is excreted unchanged. This suggests phenylpiracetam is not a prodrug for another compound (as noopept is) and that phenylpiracetam crosses the blood brain barrier intact.

PhenylPiracetam Benefits

The Russian producers of Phenotropil claim phenylpiracetam is able to fight fatigue, depression, is helpful in the treatment of epilepsy, and treatment of conditions resulting from low brain oxygen(1). Unfortunately lots of the research backing these claims up is either unavailable online or is written in Russian.  What little research is available either in full text or abstract is discussed below.

Interestingly enough, in Russia phenylpiracetam is an approved prescription drug for depression, apathy and poor attention/memory. It’s also recommended as a cognitive enhancer for Russian cosmonauts during space travel (2). This would suggest that cognitive enhancement is possible in otherwise healthy persons.

Epilepsy and Stroke Recovery

One study involving 61 patients with different forms of epilepsy compared phenotropil and AEDs (anti epilepsy drugs) vs AED’s alone. The authors concluded that the addition of phenotropil reduced seizure frequency and induced positive EEG changes.  (3) One study involving 400 patients who had recently suffered ischemic stroke showed phenylpiracetam improved recovery rate significantly when compared to placebo. (9)

Cognitive Impairment and Chronic Fatigue

The main focus of the available and translated research revolves around people with a cognitive deficit following stroke, brain injury or encephalopathy diagnosis.  One study (4) involving 99 patients with encephalopathy provided patients with a single 200mg dose per day for 30 days.  Anxiety, pain, and depression levels were notably lower after treatment.  Another study involving patients with vascular encepalopathy showed phenylpiracetam superior to no treatment (10). One US review of numerous Russian research papers confirms Phenylpiracetams ability to treat memory and attention in chronic fatigue patients and the drugs superiority over piracetam in this regard.  (2)

Stimulant Effect

One study (5) involving rodents sought to test the stimulating and cognitive enhancing properties of phenylpiracetam using passive avoidance and forced swim tests.   The R enantiomer of phenylpiracetam was found to improve retention latency by 195% while both R and S enantiomers were found to reduce immobility time (suggesting an antidepressant effect) during a forced swim test, with the high dose R enantiomer being superior to S at doing so.

Phenylpiracetam’s Mechanism Of Action

Given the structural similarity of Phenylpiracetam to phenylethylamine (6)(7) and the molecules reported stimulant properties, it’s reasonable to assume phenylpiracetam has some affinity for dopamine and noradrenaline receptors.  Indeed the manufacturers state that phenotropil  “improves regional blood flow in the ischemic areas of the brain. It increases noradrenaline, dopamine and serotonin in the brain, does not affect the level of GABA, does not bind to GABA…

Another US review of the literature suggests the same, stating “However, injection of this drug (100 mg/kg, intraperitoneally) to rats increases the numbers of both nACh and NMDA receptors, but decreases serotonin and dopamine receptors in the brain tissue” (2)

If the stimulant side of Phenylpiracetam can be attributed to phenylethylamine-like structure of the molecule, it’s likely that some of the anticonvulsant, cognitive enhancement properties of the molecule are, in part, related to the piracetam side of the molecule. While research is unclear as to the exact mechanism of action for piracetam, enhancement of cell membrane fluidity and glutamate modulation are suggested mechanisms of action. (8)

Ancedotal reports largely suggest that a tolerance to phenylpiracetam’s stimulant effects builds quickly, considering the research also confirms receptor down regulation it’s wise to assume that this nootropic should be cycled.

PhenylPiracetam Safety

The manufacturers insert suggests that phenylpiracetam shouldn’t be used during pregnancy or in children due to lack of clinical data. Caution is advised for patients with kidney or liver failure.

Lethal toxicity for extreme doses was measured at 800mg/KG in rodents suggesting a wide margin of safety. There have been no documented teratogenic, mutagenic or carcinogenic effects with phenylpiracetam (according to the manufacturers).