Phenylpiracetam is a nootropic of the racetam family (subgroup 1). Phenylpiracetam and other racetams enhance learning and memory and are used clinically in Russia to facilitate recovery from brain injuries. Phenylpiracetam is the most potent racetam, has superior bioavailability (~100%), and is considered more efficacious than piracetam.
Based on a crude analysis of its chemical structure, phenylpiracetam is a hybrid of piracetam and phenylethylamine, sharing properties of both. Anecdotally, phenylpiracteam has psychostimulatory effects which are consistent with phenylpiracetam-induced locomotor sensitization observed in rodent studies.
Phenylpiracetam (N-carbamoylmethyl-4-aryl-2-pyrrolidone (2-(2-oxo-4-phenyl-pyrrolidin-1-yl) acetamide; carphedon; phenotropil) was identified in Russia several decades ago as a nootropic agent that improves cognition.
Phenylpiracetam is a piracetam derivative with the addition of a phenyl functional group. The addition of the non-polar phenyl group to the piracetam structure results in enhanced hydrophobicity, increasing phenylpiracetam’s blood brain barrier penetration.
Remarkably, phenylpiracetam was originally used on spaceships by Russian astronauts to increase performance. More recently, phenylpiracetam has been introduced into clinical practice (in Russia).
As of 2003, the state pharmacological committee of Russian approved phenylpiracetam as a prescription drug for cerebrovascular deficiency, depression, apathy, attention and memory decline, and it is recommended for cosmonauts for increasing physical and mental/cognitive activities in space.
Highlights From The Literature
- Phenylpiracetam is beneficial for patients who develop cognitive deficits, depression, and other neuropsychiatric disorders after brain injury
- Phenylpiracetam reportedly increased quality of life in patients with encephalopathy after acute lesions, brain traumas and glioma surgery, and the average MMSE scores used to assess cognition improved in all three groups
- Phenylpiracetam alleviated anxiety and depression, and enabled patients to better execute everyday tasks
- Phenylpiracetam was superior to piracetam in the treatment of chronic vascular encephalopathy as it improved performance on all exams, whereas only 2 of 8 test scores were improved by piracetam
- Phenylpiracetam improved the scores of ten-word memory tests and attention switching tasks in patients with asthenia and chronic fatigue syndrome (CFS)
- Phenylpiracetam robustly increased the problem solving ability of adolescents with asthenia and was sperior to piracetam in combination with multivitamins and physiotherapy.
A phenyl derivative of piracetam, phenotropil or phenotropyl is absorbed fast and exhibits high oral bioavailability (Phenotropil®, product insert). Studies on rodents (100 mg/kg, intramuscular, oral) showed absorption time of ~1 hour and half-life of 2.5–3 hours, but its pharmacokinetic profiles in humans are unpublished. It demonstrates multitherapeutic potential, some in common with subgroup 2 AEDs.
Phenylpiracetam has a single chiral center at the 4th position o the pyrrolidone ring. Hence, two enantiomers (mirror images) of phenylpiracetam exist, R-phenylpiracetam and S-phenylpiracetam.
It has previously been reported that the R-phenylpiracetam is the most active enantiomer. Whereas R-phenylpiracetam significantly enhanced memory function in a passive avoidance response test at a dose of 1mg/kg, the S-phenylpiracetam lacked an effect.
Racemic phenylpiracetam in vitro binds to nicotinic acetylcholine receptors with an IC(50) of 5.86 uM. Seven-day administration of phenylpiracetam in rats significantly increased the Bmax of N-methyl-d-aspartate (NMDA) and nicotinic acetylcholine receptors
The Bmax can be used to measure the density of a receptor site in a particular preparation; hence phenylpiracetam-elicited increases in the Bmax of these receptors implies increased receptor densities.
Comparison To Other Racetams (subgroup I)
|Piracetam||Low: 50-300 mg/kg||~100%||4-5 h|
|Oxiracetam||Medium: 25-40 mg/kg||~75%||3-6 h|
|Pramiracetam||Medium: 10-20 mg/kg||~100%||2-8 h|
|Aniracetam||Medium: 12-25 mg/kg||~11%||1-2.5 h|
|Phenylpiracetam||High: 2.5-5 mg/kg||~100%||3-5 h|
The above table is populated by so-called “subgroup I racetams”, i.e., cognitive enhancing racetams. Subgroup II and subgroup III are comprised of antiepileptic racetams and uncharacterized racetams, respectively.