Phenylpiracetam

Phenylpiracetam (Phenotropil) is a racetam drug derived from Piracetam in where the only modification is the addition of a phenyl group to its structure. It appears to require much lower doses for similar properties, and appears to have psychostimulatory effects.

This page features 19 unique references to scientific papers.

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Summary

All Essential Benefits/Effects/Facts & Information

Phenylpiracetam (Phenotropil) is a Nootropic of the Racetam family, and as its name suggests it is a phenyl- derivative of Piracetam. Phenylpiracetam is reported to be more neuroprotective than piracetam is, but also possesses psychostimulatory properties and is reported to enhance physical performance.

There is a fair bit of research to suggest that phenylpiracetam is effective, like other racetam drugs, in attenuating the rate of and symptoms of cognitive decline. Many of these studies use phenylpiracetam for over one month's time, and the benefits seen may only apply to organic causes of cognitive decline (dementia and stroke) rather than traumatic brain injury.

There is only one rat study noting cognitive enhacement in otherwise healthy young rats, and this study only noted benefit with the R-isomer (the racemic mixture, which is commonly sold, failed to outperform control). While cognitive enhancing propertes of phenylpiracetam in youth cannot be ruled out, they are possibly distinct from the psychostimulatory properties (which occur with said racemic mixture and the R-isomer).

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Things To Know

Also Known As

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

Do Not Confuse With

Piracetam (Parent molecule)

Things to Note

  • Phenylpiracetam is banned by the World Anti-Doping Agency (Olympics) due to its reported psychostimulatory and cold resistance properties

How to Take

Recommended dosage, active amounts, other details

Phenylpiracetam is taken at a dosage of 100-200mg acutely, and this dose is taken 2-3 times per day (totalling a daily range of 200-600mg). The lower range seems effective, but the optimal dosage is not yet known.

The R-isomer appears to be more active on the common usages of phenylpiracetam (stimulation and cognition) than does the S-isomer, and while the racemic mixture (commonly sold version) is effective for cognitive decline it is not certain if it works for nootropic purposes in youth.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects phenylpiracetam has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
Cognition Minor Very High See all 3 studies
Cognition is improved in persons suffering from cognitive decline, organic brain lesions, and epilepsy. There are currently no studies conducted in otherwise healthy youth for the purpose of cognitive enhancement
Functionality in Elderly or Injured Minor - See study
Physical function and activities of daily living in elderly persons after a stroke appear to be benefitted with phenylpiracetam. While it should work in elderly persons without cognitive impairment, this has not been tested
Stroke Recovery Rate Minor - See study
Symptoms (cognitive and physical) seen after a stroke appear to be more rapidly recovered with daily usage of phenylpiracetam than with placebo
Anxiety Minor - See study
Anxiety as a symptom of stroke has been reduced with phenylpiracetam. No studies currently exist in otherwise healthy persons with anxiety symptoms
Cognitive Decline Minor - See study
The rate of cognitive decline appears to be significantly reduced following usage of phenylpiracetam
Depression Minor - See study
Depressive symptoms following a stroke appear to be reduced following ingestion of phenylpiracetam. Currently, there are no studies on otherwise healthy persons with depressive symptoms
Fatigue - - See study
Despite the usage of phenylpiracetam to treat asthenia, the lone study assessing this in persons with traumatic brain injuries failed to find a benefit (which may be a false negative if phenylpiracetam is inactive on brain injuries in the first place).


1Sources and Structure

1.1. Sources

Phenylpiracetam (structual name (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide and the brandname of either Phenotropil or Carphedon) is a Piracetam derivative that has an additional phenyl group at position 4 of the 2-oxopyrrolidine ring. It is reported (from the manufacturer) to be rapidly and well absorbed due to the enhanced lipophilicity[1] and exerts more anti-amensiac, neuroprotective, and stimulatory effects than does piracetam[2]|published=2007 Mar-Apr|authors=Tiurenkov IN, Bagmetov MN, Epishina VV|journal=Eksp Klin Farmakol][3] and has been reported to enhance physical performance and cold resistance[4] leading to it being included in the banned substances list of the world anti-doping agency (WADA, listed under 4-phenylpiracetam or carphedon as a non-specified stimulant).[5]

Phenylpiracetam is a derivative of piracetam that is touted for being more effective in its anti-amnesiac properties and also possessing psychostimulatory properties

1.2. Structure

Phenylpiracetam is the piracetam structure with an additional phenyl group attached to the pyrrolidone nucleus, albeit at a different steric location than the substituted phenyl groups seen on Aniracetam or Nefiracetam. Due to the chiral center at the fourth position of the pyrrolidinone ring, it can exist in an S or R isomer; the clinically used form is the racemic mixture.[6]

Phenylpiracetam, as the name implies, is piracetam with a phenyl group attached to it


2Pharmacology

2.1. Serum

Injections of 100mg/kg phenylpiracetam to rodents exhibits a half-life of 2.5-3 hours.[7]

30 minutes following a 25mg/kg injection, phenylpiracetam can be detected in the brain at 67-73µg/g and a later test using 100mg/kg noted that approximately 1% of injected phenylpiracetam reached the brain.[6]

No oral pharmacokinetic studies have been conducted yet, but it does appear to be able to cross the blood brain barrier


3Neurology

3.1. Cognition

Phenylpiracetam appears to have a series of trials conducted on it (Cited vicariously through this review[1] where four of seven can be located online[8][9][10][11][12]) showing improvement in cognition in persons with cognitive decline from organic causes, with one study noting a minor improvement in cognition in those with epilepsy (youth)[11] and the lone failure coming from a study on traumatic brain injury in youth.[10] These studies used a dosage range between 200mg (100mg twice daily) up to 600mg (200mg thrice daily), and all lasted for one months time.

Symptoms associated with cognitive decline such as anxiety and depression have also been noted to be reduced in open-label trials[9] although the study assessing asthenia (weakness; one of the major reasons phenylpiracetam is prescribed) failed to find a significant effect over control (mild cranial trauma).[10]

One trial not included in the aforementioned review[13] noted improvement in function (physical and cognitive) in person's who suffered from strokes when phenylpiracetam was taken at 400mg daily for one years time.

A relatively large body of research based in Russia (much of which is not available online in the west) appears to support phenylpiracetam for the purpose of attenuating or treating organic cognitive decline. There are no studies currently in youth using phenylpiracetam for cognitive enhancement, and the benefit seen in organic cognitive decline may not extend to physical trauma (like Noopept has been noted in helping)

Only one study has been conducted in otherwise healthy rats, and the R-isomer (not racemic mixture) of phenylpiracetam at 1mg/kg and 10mg/kg improved retention latency in a passive avoidance test by 195% and 185%, respectively.[6]

The R-isomer may have cognitive enhancing properties

3.2. Depression

Depressive symptoms in a forced-swim test in rats have been noted to be greatly reduced with 50-100mg/kg phenylpiracetam, with the R-isomer being more active than the S-isomer.[6] Elsewhere, the depressive symptoms in persons with cognitive decline have been attenuated in an open-label trial with 200mg phenylpiracetam daily (100mg twice daily).[9]

Although not well researched, phenylpiracetam does appear to have anti-depressant properties that are seen with the racemic mixture but more potently with the R-isomer in particular

3.3. Psychostimulation

In rats injected with phenylpiracetam, 10-50mg/kg appears to increase locomotor activity (distance and velocity) mostly due to the R-isomer and without any apparent dose-dependence.[6] The 50mg/kg dose lasted for approximately four hours when the R-isomer was used, and the racemic mixture lasted for two hours.[6]

One study has reported sleep disturbances as a side-effect of phenylpiracetam (Sazonov et al. 2006; not located online but cited via this review[1]), in accordance with the reported psychostimulatory properties. Other trials do not note such a side-effect, and the reason it was detected in this study only is unknown.

Although not well investigated, there is some evidence for the psychostimulatory properties of phenylpiracetam hindering sleep


4Inflammation and Immunology

4.1. Interventions

25mg/kg of phenylpiracetam injections daily for five days to rats subsequently given lipopolysaccharide (LPS) injections to aggravate the immune system noted that LPS-induced alterations in DTHR and phagocytosis were normalized with no apparent effect on antibody production.[14] Behavioural alterations from LPS injections (anxiety and sluggishness) were fully abolished.[14]

Although not well researched at this point in time, phenylpiracetam may possess immunosupportive properties under periods of immune stress

Scientific Support & Reference Citations

References

  1. Malykh AG, Sadaie MR Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders . Drugs. (2010)
  2. [Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia
  3. Bobkov IuG, et al Pharmacological characteristics of a new phenyl analog of piracetam--4-phenylpiracetam . Biull Eksp Biol Med. (1983)
  4. Kim S, et al Determination of carphedon in human urine by solid-phase microextraction using capillary gas chromatography with nitrogen-phosphorus detection . Analyst. (1999)
  5. List of Prohibited Substances and Methods. S6. Stimulants
  6. Zvejniece L, et al Investigation into stereoselective pharmacological activity of phenotropil . Basic Clin Pharmacol Toxicol. (2011)
  7. Experimental pharmacokinetics of carphedon
  8. Gustov AA, et al Phenotropil in the treatment of vascular encephalopathy . Zh Nevrol Psikhiatr Im S S Korsakova. (2006)
  9. Savchenko AIu, Zakharova NS, Stepanov IN The phenotropil treatment of the consequences of brain organic lesions . Zh Nevrol Psikhiatr Im S S Korsakova. (2005)
  10. Kalinskiĭ PP, Nazarov VV Use of phenotropil in the treatment of asthenic syndrome and autonomic disturbances in the acute period of mild cranial brain trauma . Zh Nevrol Psikhiatr Im S S Korsakova. (2007)
  11. Lybzikova GN, Iaglova ZhS, Kharlamova IuS The efficacy of phenotropil in the complex treatment of epilepsy . Zh Nevrol Psikhiatr Im S S Korsakova. (2008)
  12. Gerasimova MM, Chichanovskaia LV, Slezkina LA The clinical and immunological aspects of the effects of phenotropil on consequences of stroke . Zh Nevrol Psikhiatr Im S S Korsakova. (2005)
  13. Koval'chuk VV, et al Efficacy of phenotropil in the rehabilitation of stroke patients . Zh Nevrol Psikhiatr Im S S Korsakova. (2010)
  14. Samotrueva MA, et al Psychoimmunomodulatory effect of phenotropil in animals with immune stress . Bull Exp Biol Med. (2011)
  15. Koval'chuk VV, et al Efficacy of phenotropil in the rehabilitation of stroke patients . Zh Nevrol Psikhiatr Im S S Korsakova. (2010)
  16. Gustov AA, et al Phenotropil in the treatment of vascular encephalopathy . Zh Nevrol Psikhiatr Im S S Korsakova. (2006)
  17. Savchenko AIu, Zakharova NS, Stepanov IN The phenotropil treatment of the consequences of brain organic lesions . Zh Nevrol Psikhiatr Im S S Korsakova. (2005)
  18. Kalinskiĭ PP, Nazarov VV Use of phenotropil in the treatment of asthenic syndrome and autonomic disturbances in the acute period of mild cranial brain trauma . Zh Nevrol Psikhiatr Im S S Korsakova. (2007)
  19. Lybzikova GN, Iaglova ZhS, Kharlamova IuS The efficacy of phenotropil in the complex treatment of epilepsy . Zh Nevrol Psikhiatr Im S S Korsakova. (2008)