Phenylpiracetam, also known as Carphedon or Phenotropyl was initially developed in Russia during the early 1990s. Its mechanisms was first describes on a Russian study on 1983. Later, it was produced under the brand name “CARPHEDON” on a Russian research institute. It was primarily given to the Russian military and astronauts to enhance their work aptitude.
On the latter years, it was used by international athletes as a doping control to enhance one’s endurance and skills. Thus, the Word Anti-Doping Agency included it on the list of prohibited substances to prevent an athlete from gaining an edge over others ,  on 1998. Phenylpiracetam use gained approval from the Russian authorities in 2003 as a prescription drug for the enhancement of cognitive and physical skills of individuals with somatic and memory problems.
Carphedon is a derivative of piracetam. It is structurally comparable to its parent compound as well as on other piracetam derivatives (e.g. aniracetam, nefiracetam). A benzene (phenyl) ring was purportedly added on its structure to potentiate/enhance its effects more than that of piracetam. Phenylpiracetam can exist as two different enantiomers; nevertheless, it is typically used as a racemic compound. This nootropic agent has higher bioavailability and is quite more potent compared to other racetams.
Mechanism of action
The mechanism of action of phenylpiracetam is unclear. However, in a recent study done by Basic and Clinical Pharmacology and Toxicology, an investigation of carphedon’s “stereoselective pharmacological activity” was carried out. This study tried to explain how it works and how it is different from other piracetam like drugs.
Phenylpiracetam can be separated into two different enantiomers – R- and S- enantiomer. The S- enantiomer is claimed to be responsible on leviteracetam’s anti-convulsant action. This study revealed that R- enantiomer was the most active substance found in phenylpiracetam exerting significant effects on memory improvement, locomotor activities (e.g. muscle strength, motor coordination) and anti-depressant activities through increasing the density of nicotinic acetylcholine, GABA, dopamine and N-methyl-D-aspartate receptors. These receptors are involved in memory and overall cognition process , , .
Most, if not all human trials conducted to measure the effects of phenylpiracetam are exclusively performed in Russia. Some of these studies indicated the different therapeutic effects of this particular nootropic agent.
One of the benefits associated with phenotropil includes improvement on individuals suffering with depression and cognitive problems after brain injuries and encephalopathy. In an open label study, 99 individuals (40 to 60 y/o) diagnosed with encephalopathy after developing acute lesions from brain traumas, gliomas surgery and cerebral blood circulation have been deliberated. Patients were given 200 mg of phenylpiracetam daily within a month.
After data collection, Mine Mental State Examination (MMSE) scores – a standard questionnaire for cognition assessment improved significantly on all patients. Participants displayed increased mobility and lesser discomfort. Depression symptoms and anxiety was significantly improved. Even EEG study indicates that the alpha beta rhythms are normalizing .
In a similar study, 51 subjects diagnosed with encephalopathy of vascular origins were treated with phenylpiracetam and piracetam. Results indicated that phonilypiracetam is more potent as it was able to improve cognitive performance on all neurological and psychological tests .
Chronic fatigue syndrome (CFS) and asthenia treatment
A comparative trial involving chronic fatigue syndrome and asthenia patients were carried out. A total of 180 patients were treated with phenyl piracetam, piracetam and placebo for a month. Subjects were assess using attention and memory tests revealing significant improvement amongst those who took phenylpiracetam relative to placebo and 87% of CFS patients and 83% of asthenic patients responded considerably to phenylpiracetam versus 55% and 48% respectively to piracetam .
This positive result was replicated on another study involving adolescents diagnosed with asthenic syndrome. Subjects were given phenylpiracetam for 1 month. Phenylpiracetam significantly increased the problem solving skills better than that of piracetam .
In animal studies, phenylpiracetam showed positive affinity as an antiepileptic drug. A group of researchers decided to replicate these studies using human examples. As such, 61 individuals were enlisted as subjects. They were given phenylpiracetam for 2 months in conjunction with one standard anti-epileptic medication. Results showed that there is a substantial decrease on seizure frequency. Seizure remission improved moderately .
A double-blind study involving 40 epileptic subjects showed consistent results. Subjects were treated with phenylpiracetam for a month. Assessment was done using the Mini Mental State Examination (MMSE) scale revealing the improvement of overall cognitive performance. The studies indicate that phenylpiracetam is an excellent adjunct therapy for epilepsy .
A placebo controlled study was done to assess the efficacy of phenylpiracetam in the treatment of stroke patients. 400 patients diagnosed with ischemic stroke were divided into 2 groups. 200 patients received three course of phenylpiracetam a year after the stroke while the other help received the control drug. All patients were assessed using different neurologic function scales. Analysis of the results revealed that the rehabilitation of activities of daily living (ADLs) and neurologic functions was significantly improved on the phenylpiracetam group . Results of another study involving ischemic stroke patients yielded substantial improvement on stroke severity and Mini Mental State Examination (MMSE) scores and an inclination towards ADL’s.
As a neuroprotective agent, phenylpiracetam has the ability to prevent and delay ganglial cell death. And since ganglial apoptosis and optical neuropathy is the culprit of blindness in glaucoma, an open label study regarding the effects of phenylpiracetam on vision acuity was done. 26 individuals diagnosed with unstable open angle glaucoma were recruited as subjects. Subjects were given doses of phenylpiracetam for a month. Analysis of results showed tht visual acuity impairment and blind spots statistically decreased glaucoma on patients. Additionally, 80% of the patients exhibited stabilized glaucoma after the follow-up period .
These studies revealed favorable results towards the efficacy of phenylpiracetam in treating encephalopathy, chronic fatigue syndrome, asthenia, epilepsy, stroke and glaucoma. Nevertheless, these evidences are not enough to conclude the safety and efficacy of this drug. Hence, further human studies are warranted.