What is Phenylpiracetam? Everything you wanted to know

Racetams

You may have heard of nootropics, but not specifically about this class of compound.  Racetams are a diverse group of compounds with similar pharmacology and wildly different potential applications.  For example, levetiracetam has been used a a treatment for seizure disorders and is a racetam that activates the synaptic vesicle 2A receptor. (1) This is unlike the group of racetams that we are most concerned with here.

Phenylpiracetam

The discussion here is about phenylpiracetam in particular.  After examining all of the research available, phenylpiracetam seems to potentially be the most effective for a wide range of applications.

Phenylpiracetam has been around since the early 80's.  The first mention in the literature is a 1983 paper "Pharmacological characteristics of a new phenyl analog of piracetam--4-phenylpiracetam."  The study is in Russian, but the English abstract states that it "was found to (improve motivation), to remove psycho-depressant effects of diazepam, to inhibit (dizziness from spinning), and to prevent the development of retrograde amnesia" (amnesia of events prior to trauma or damage).

 

Cognitive Function

 While no direct evidence of cognitive enhancement among healthy individuals with phenylpiracetam use exists as of the time of this article, there are studies we can look at to infer expected results.

A 2002 meta-analysis concluded that "difference between those individuals treated with piracetam and those given placebo... the results of this analysis provide compelling evidence for the global efficacy of piracetam in a diverse group of older subjects with cognitive impairment" (2)

Phenylpiracetam is a derivative of piracetam, as are the other racetams.  It is also known as Phenotropil and is referred to as such in many of these studies.  One study was conducted using randomized controlled trials with 90 participants  evaluating the efficacy of adding phenylpiracetam to epilepsy patients treatment regimen. (3)  " Phenotropil reduced the frequency of seizures and improved cognitive function..."

Another study in 2010 concluded that treatment group given 400mg/day of Phenotropil (quite a large dose by nootropic standards) showed significant improvements compared with the control group. (4)

Phenylpiracetam hows been shown clinically to improve outcomes for patients with several different types of brain trauma.  It has also been shown to have neruo-protective effects in several studies.  A study was done on wistar rats comparing piracetam to phenylpiracetam. They had blood flow to the brain blocked.  The animals that were administered phenylpiractem and (to a lesser extent) piracetam "reduced the extent of neuralgic deficiency manifestations, retained the locomotor, research, and memory functions in animals with gravitational cerebral ischemia, increased the survival of experimental animals, and favored the restoration of local cerebral flow upon the occlusion of carotid arteries."(5)  While it is not totally clear that phenylpiracetam can improve memory or higher function in healthy young individuals, it seems clear that it may have some potential to prevent future decline. 

Motivation

 Another potential benefit, of phenylpiracetam in particular, is the increase in motivation it seems to promote.  Phenylpiracetam has two optical isomers that have been looked at independently.  Both S-phenylpiracetam and R-phenylpiracetam have been shown to be dopamine transporter inhibitors.  The   S-phenylpiracetam study showed reductions in body fat gain in overfed mice, as well as lower levels of leptin and lowered hyperglycemia. (6)  In the R-phenylpiracetam study, "A single...injection of (R-phenylpiracetam) significantly attenuated the ... overexpression of inflammatory genes, such as tumour necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β)."  Phenylpiracetam is sold as a racemic mixture of the two isomers, and looking at their independant actions can give us some clues as to their combined effect.

One russion study comparing different nootropics and their effects noted that in addition to nootropic effects and a reduction in anxiety that was noted with many other compounds,  "phenotropil additionally increased locomotor activity." (7)

Toxicity

No LD50 data is available for phenylpiracetam. In reading of all the research, no toxicity was mentioned in dosages meaningful to humans.  However, this does not mean that this compound is inherently safe.  It seems to be non-toxic in the short term, but no data is available for long term periodic or chronic use.  As per usual, I recommend getting blood-work to evaluate liver and kidney function a month or two into any new regimen to assess your body's reaction.  This is in addition to at least bi-yearly blood-work to establish a baseline. 

Conclusion

 The method of action for these compounds is still a little ambiguous.  Some evidence for the basic action of racetams exists in studies of piracetam.  While not actually agonizing the muscarinic acetylcholine receptors, it has been shown to up-regulate their density in aged mice but not in young mice.(8)  This is consistent with nootropics experimenters preferring to stack a choline supplement with a racetam to achieve optimal results. 

At this time, and with the current level of research, I would still consider it a somewhat risky endeavor to add phenylpiracetam into your regimen.  While a decent amount of research is available in totality, when talking about phenlypiracetam in particular there is not much research aside from some animal studies.  While it is possible to assume that phenylpiracetam is harmless based on circumstantial evidence, I would definitely consider it somewhat risky to use a compound not thoroughly tested for safety in humans, particularly for long term continuous use. 

 With that said, these compounds show amazing promise for a vast array of clinical applications.  Anything we can find to slow down or potentially reverse age-related, disease-related, and traumatic-injury related cognitive decline has massive implications.  In the future perhaps a whole new working class of older folks with sharp cognition could provide value, and produce even more wealth for modern society.  With so many willing experimenters, and so many promising compounds to explore, our twilight years may not be so grim a prospect in the coming decades. 

-James S.

 

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References

(1) Malykh AG, Sadaie MR. Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. Drugs. 2010 Feb 12;70(3):287-312. doi: 10.2165/11319230-000000000-00000. PMID: 20166767.

 (2) Waegemans T, Wilsher C, R, Danniau A, Ferris S, H, Kurz A, Winblad B: Clinical Efficacy of Piracetam in Cognitive Impairment: A Meta-Analysis. Dement Geriatr Cogn Disord 2002;13:217-224. doi: 10.1159/000057700

 (3) Grebeniuk OV, Zhukova NG, Alifirova VM. Éffektivnost' dopolnitel'noĭ terapii fenotropilom pri lokal'no-obuslovlennoĭ épilepsii u vzroslykh [The efficacy of add-on treatment with phenotropil in adult patients with locally-induced epilepsy]. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(11 Pt 2):27-31. Russian. doi: 10.17116/jnevro201411411227-31. PMID: 25591651.

(4) Koval'chuk VV, Skoromets AA, Koval'chuk IV, Stoianova EG, Vysotskaia ML, Melikhova EV, Il'iaĭnen EV. [Efficacy of phenotropil in the rehabilitation of stroke patients]. Zh Nevrol Psikhiatr Im S S Korsakova. 2010;110(12 Pt 2):38-40. Russian. PMID: 21626817.

(5) Tiurenkov IN, Bagmetov MN, Epishina VV. [Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia]. Eksp Klin Farmakol. 2007 Mar-Apr;70(2):24-9. Russian. PMID: 17523446.

(6) Zvejniece L, Svalbe B, Vavers E, Makrecka-Kuka M, Makarova E, Liepins V, Kalvinsh I, Liepinsh E, Dambrova M. S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity. Pharmacol Biochem Behav. 2017 Sep;160:21-29. doi: 10.1016/j.pbb.2017.07.009. Epub 2017 Jul 22. PMID: 28743458.
(7) Samotrueva MA, Tyurenkov IN, Teplyi DL, Serezhnikova TK, Khlebtsova EB. Psychoimmunomodulatory effect of phenotropil in animals with immune stress. Bull Exp Biol Med. 2011 May;151(1):51-4. doi: 10.1007/s10517-011-1257-4. PMID: 22442801.
(8) Pilch H, Müller WE. Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice. Psychopharmacology (Berl). 1988;94(1):74-8. doi: 10.1007/BF00735884. PMID: 3126530.

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