Phenylpiracetam

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Phenylpiracetam
Fonturacetam.svg
Phenylpiracetam.png
Clinical data
Trade names Phenotropil; Carphedon
Pregnancy
category
  • Unknown
Routes of
administration
Oral (tablets)
ATC code
  • None
Legal status
Legal status
  • Legal
    ℞-only (RU)
Pharmacokinetic data
Bioavailability ~100%
Metabolism None
Biological half-life 3–5 hours
Excretion Urine (~40%), bile and perspiration (~60%)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard 100.214.874
Chemical and physical data
Formula C12H14N2O2
Molar mass 218.3 g/mol
3D model (Jmol)
Chirality Racemic mixture
Boiling point 486.4 °C (907.5 °F)
 NYesY (what is this?)  (verify)

Phenylpiracetam (INN: fonturacetam,[1] brand names Phenotropil, Carphedon), also called is a phenylated analog of the drug piracetam which was developed in 1983 in Russia where it is available as a prescription drug. Research on animals has indicated that phenylpiracetam may have anti-amnesic, antidepressant, anticonvulsant, anxiolytic, and memory enhancement effects.[2][3]

Uses[edit]

A few small clinical studies have shown possible links between prescription of phenylpiracetam and improvement in a number of encephalopathic conditions, including lesions of cerebral blood pathways, traumatic brain injury and certain types of glioma.[4]

Phenylpiracetam reverses the depressant effects of the benzodiazepine diazepam, increases operant behavior, inhibits post-rotational nystagmus, prevents retrograde amnesia, and has anticonvulsant properties.[2][5][6]

Phenylpiracetam is typically prescribed as a general stimulant or to increase tolerance to extreme temperatures and stress.[7]

Phenylpiracetam has been researched for the treatment of Parkinson's disease.[8]

Animal Model Research[edit]

In Wistar rats with gravitational cerebral ischemia, Phenylpiracetam reduced the extent of neuralgic deficiency manifestations, retained the locomotor, research, and memory functions, increased the survival rate, and lead to the favoring of local cerebral flow restoration upon the occlusion of carotid arteries to a greater extent than did piracetam.[9]

Operant behavior[edit]

Phenylpiracetam is known to increase operant behavior. In tests against a control, Sprague-Dawley rats given free access to less-preferred rat chow and trained to operate a lever repeatedly to obtain preferred rat chow performed additional work when given methylphenidate, d-amphetamine, and phenylpiracetam. Rats given 1 mg/kg amphetamine performed an average of 150% as much work and consumed 50% as much non-preferred rat chow than control rats; rats given 10 mg/kg Methylphenidate performed 170% as much work and consumed similarly; and rats given 100 mg/kg Phenylpiracetam performed an average of 375% as much work, and consumed little non-preferred rat chow.

Present data show that (R)-phenylpiracetam increases motivation, i.e., the work load, which animals are willing to perform to obtain more rewarding food. At the same time consumption of freely available normal food does not increase. Generally this indicates that (R)-phenylpiracetam increase motivation [...] The effect of (R)-phenylpiracetam is much stronger than that of methylphenidate and amphetamine.[10]

Pharmacology[edit]

Phenylpiracetam binds to α4β2 nicotinic acetylcholine receptors in the mouse brain cortex with IC50 = 5.86 μM.[5]

In rats, scopolamine is used to model memory impairment. It impairs performance in the conditioned passive avoidance reflex test, increases cortical nACh and hippocampal NMDA receptor densities, and decreases striatal D1 and cortical benzodiazepine receptor densities. Phenylpiracetam demonstrates antiamnestic activity by restoring performance in the passive avoidance test and partially reversing each of these scopolamine-induced receptor density changes.[5]

Experiments performed on Sprague-Dawley rats in a European patent for using Phenylpiracetam to treat sleep disorders showed an increase in extracellular dopamine levels after administration. The patent asserts discovery of phenypiracetam's action as a dopamine reuptake inhibitor[10] as its basis.

The peculiarity of this invention compared to former treatment approaches for treating sleep disorders is the so far unknown therapeutic efficacy of (R)-phenylpiracetam, which is presumably based at least in part on the newly identified activity of (R)-phenylpiracetam as the dopamine re-uptake inhibitor

Phenylpiracetam may also act as a noradrenaline reuptake inhibitor, making it an NDRI.[5]

Availability[edit]

Phenotropil
Phenotropil 100 mg from Russia

While not prescribed as a pharmaceutical in the West, in Russia it is available as a prescription medicine under the name Phenotropil (but most drugstores sell it without prescriptions).[citation needed]

Phenylpiracetam is not scheduled by the DEA in the U.S.[11]

Phenylpiracetam is readily-synthesized commercially. To avoid the problem of attaching the phenyl group to piracetam at position 5 rather than 3 or 4, commercial syntheses cyclizes phenibut by replacing the hydroxide with a hydrogen to create a pyrrole group and then reacting bromoacetic acid and ammonia to replace the bromine with the nitrogen on the pyrrole. This produces a racemic phenylpiracetam, which then undergoes purification to produce the final product.

Athlete doping[edit]

Because it increases physical stamina and provides improved tolerance to cold weather, it appears on the lists of stimulants banned for in-competition use by the World Anti-Doping Agency. This list is applicable in all Olympic sports.

See also[edit]

References[edit]

  1. ^ "WHO Drug Information, Vol. 24, No. 1, 2010" (PDF). p. 56. Retrieved 31 December 2015. 
  2. ^ a b Malykh, A. G.; Sadaie, M. R. (2010). "Piracetam and Piracetam-Like Drugs". Drugs. 70 (3): 287–312. PMID 20166767. doi:10.2165/11319230-000000000-00000. 
  3. ^ Zvejniece L, Svalbe B, Veinberg G, Grinberga S, Vorona M, Kalvinsh I, Dambrova M (2011). "Investigation into stereoselective pharmacological activity of phenotropil.". Basic & Clinical Pharmacology & Toxicology. 109 (5): 407–12. PMID 21689376. doi:10.1111/j.1742-7843.2011.00742.x. 
  4. ^ Savchenko, A. I.; Zakharova, N. S.; Stepanov, I. N. (2005). "The phenotropil treatment of the consequences of brain organic lesions". Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 105 (12): 22–26. PMID 16447562. 
  5. ^ a b c d Firstova, Yu. Yu.; Abaimov, D. A.; Kapitsa, I. G.; Voronina, T. A.; Kovalev, G. I. (2011). "The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task". Neurochemical Journal. 28 (2): 130–141. doi:10.1134/S1819712411020048. 
  6. ^ Bobkov, I.; Morozov, I. S.; Glozman, O. M.; Nerobkova, L. N.; Zhmurenko, L. A. (1983). "Pharmacological characteristics of a new phenyl analog of piracetam--4-phenylpiracetam". Biulleten' eksperimental'noi biologii i meditsiny. 95 (4): 50–53. PMID 6403074. 
  7. ^ Kim, S.; Park, J. H.; Myung, S. W.; Lho, D. S. (1999). "Determination of carphedon in human urine by solid-phase microextraction using capillary gas chromatography with nitrogen-phosphorus detection". The Analyst. 124 (11): 1559–1562. PMID 10746314. doi:10.1039/a906027h. 
  8. ^ WO application 2014005721A1, Hermann Russ; Andrzej Dekundy & Wojciech Danysz, "Use of (r)-phenylpiracetam for the treatment of parkinson's disease", published 2014-01-09 
  9. ^ Tiurenkov IN, Bagmetov MN, Epishina VV (2007). "Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia". Eksp Klin Farmakol. 70 (2): 24–29. PMID 17523446. 
  10. ^ a b EP application 20140000021, "Use of (r)-phenylpiracetam for the treatment of sleep disorders", published 2015-07-08 
  11. ^ List of Controlled Substances