Phenylpiracetam

Structure:

Nomenclature: (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide or N-carbamoylmethyl-4-phenyl-2-pyrrolidone

Synonyms: 4-phenylpiracetam, phenylpiracetam, carphedon, carphedone, carfedone, entrop, phenotropil, fenotropil, phenotropyl.

History:

Though it is claimed in some places that it was “developed in Russia at the beginning of [the] 1990s”, [1] the activity of phenylpiracetam was first described in a Soviet scientific journal in 1983. [2]
It was then unofficially produced under the name “Carphedon” “on a small scale at a research institute of cosmic medicine in Russia”, [3] from where it was distributed to cosmonauts and the military to increase their work capacity, [4] though it subsequently found its way into the hands of athletes who were discovered to be using it to circumvent doping controls in international figure skating and athletics competitions in 1997. [3][5][6]
In 1998 it was added to the World Anti-Doping Agency list of prohibited substances. [7][8]

Phenylpiracetam was approved for use by the State Pharmacological Committee of Russia in 2003 for the treatment of certain mental disorders and cognitive impairment, [9] and is currently sold under the trade name Phenotropil as a prescription-only medicine to enhance cognitive capabilities and physical functioning of patients in Russia. [9][4]
It is also manufactured and sold by OLFA in Latvia under the trade name Entrop. [10]

Structure and Effect:

Phenylpiracetam’s unique CNS stimulating [4] and conventional nootropic effects stem from the fact that it is somewhat of a structural conjunction of phenylethylamine (a neurotransmitter in the central nervous system) and piracetam. [3]


[3]

In rat ex vivo experiments, phenylpiracetam has been found to bind to the nicotinic acetylcholine receptors and significantly increase the Bmax (density) of NMDA receptors, nicotinic acetylcholine receptors, GABAA receptors and dopamine (D1, D2, and D3) receptors, although it does not bind to dopamine or seratonin receptors. [9][11][12]

Although phenylpiracetam can exist in two separate enantiomeric forms (because of its 1 asymmetric carbon atom), it is typically clinically used as a racemic mixture. [4]
However, the R-enantiomer has been found to be the most active enantiomer with regard to antidepressant and memory-improving properties and has been patented as an antidepressant, stress-protective agent, muscle relaxant, analgesic, and “modulator of locomotor activity”. [4][13]

In comparison to other racetams, phenylpiracetam is quite potent and highly orally bioavailable. [9] Its half life is around 3-5 hours in humans. [9]

Metabolism:

Phenylpiracetam’s main metabolic biotransformations involve hydroxylation on the phenyl and heterocyclic ring after oral administration. [1] Two metabolites were identified as “3-hydroxycarphedone” and “4′-hydroxycarphedone”. [1]

Effects:

  • Phenylpiracetam was roughly as effective as piracetam in reducing motion sickness (as measured in guinea pigs that had been spun round). [2]
  • It can also prevent the development of amnesia induced in rats by electric shocks. [2]
  • A more recent study supported the anti-amnesiac properties of phenylpiracetam in rats, as measured by the abolition of amnesia induced by the anti-cholinergic drug scopolamine in the passive avoidance task. [12]
  • It was found to increase locomotor and antidepressant activity and improve memory in rats. [4]
  • Phenotropil has been found to suppress the anxiety and fear response in rats with induced immune stress. [14]
  • Phenylpiracetam was found to improve memory, attention-switching, and problem-solving skills in patients with asthenia. [9][15][16]
  • Phenotropil was reported to cause sleep disturbance in some individuals, [9][17] more than likely as a result of its stimulant-like effects.

“Super speed”; Vice Magazine Vol. 13,#4

Availability:

Although theoretically a prescription-only drug in Russia, many pharmacists will dispense it on request.
Phenylpiracetam is now available in the UK and US as Antaeus Labs Demiurge.

References
[1] Recent advances in doping analysis (6) 1999 337-348
[2] Biull Eksp Biol Med. 1983 Apr;95(4):50–3.
[3] Recent advances in doping analysis (6) 1999 349-359
[4] Basic Clin. Pharmacol. Toxicol. 2011 Nov;109(5):407–12.
[5] Doping in Sports By Detlef Thieme, Peter Hemmersbach
[6] Rechtsmedizin. 1999 Sep 16;9(6):215–7.
[7] WADA Prohibited List 2012
[8] Br J Pharmacol. 2008 Jun;154(3):606–22.
[9] Drugs. 2010 Feb 12;70(3):287-312
[10] OLFA product information: Entrop
[11] Clin Pharm 2007;4:22–6.
[12] Neurochemical Journal Volume 5, Number 2 (2011), 115-125
[13] US Patent 20100022784: N-Carbamoylmethyl-4-(R)-Phenyl-2-Pyrrolidinone, Method of its Preparation and Pharmaceutical Use
[14] Bull Exp Biol Med. 2011 May;151(1):51-4.
[15] Nervnye Bolezni 2004; 3: 28-32
[16] Nervnye Bolezni 2006; 2: 27-8
[17] Nervnye Bolezni 2006; 4: 18-21