Carphedon

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Structural formula
Structural formula of Carphedon
Structural formula without stereochemistry
General
Surname Carphedon
other names
  • ( RS ) -2- (4-phenyl-2-oxopyrrolidin-1-yl) acetamide
  • (±) -2- (4-Phenyl-2-oxopyrrolidin-1-yl) acetamide
  • Phenylpiracetam
  • Fonturacetam
Molecular formula C 12 H 14 N 2 O 2
External identifiers / databases
CAS number 77472-70-9
EC number 688-268-0
ECHA InfoCard 100.214.874
PubChem 132441
Wikidata Q420882
properties
Molar mass 218.26 g mol −1
safety instructions
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302-315-319-335
P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Carphedon , also phenylpiracetam , is a phenyl derivative of the nootropic piracetam . It increases physical performance and raises the tolerance level against cold and stress . Animal research has shown evidence of antiamnesic , antidepressant , anticonvulsant , antipsychotic , anxiolytic, and  memory enhancing effects. Carphedon is considered a designer stimulant and is on the doping list . Like bromantane , carphedon was probably developed in Russia in the 1980s for military use and sport.

pharmacology

Few small clinical studies have shown possible links between prescribing Carphedon and improvement of some encephalopathic conditions, such as cerebral blood vessel lesions , traumatic brain injury,  and certain types of glioma .

Carphedon reverses the  central depressant  effect of the benzodiazepine diazepam , improves operational behavior, reduces post-rotational nystagmus , protects against retrograde amnesia and has anticonvulsant  properties.

In  Wistar rats  with gravitation-dependent cerebral ischemia, it reduced the extent of manifestations of neuralgic deficits, stabilized locomotor , exploration and memory functions, increased the survival rate and promoted restoration of local cerebral blood flow in occlusion of carotid arteries  more than piracetam did.

In rats, it led to reduction in the number of nACh - and  NMDA receptors and increasing the density of  D 1 - , D 2 - and D 3 receptors.

doping

By February 2006, sixteen athletes had been convicted of doping with Carphedon, including in March 2005 professional cyclist Danilo Hondo from the Gerolsteiner team. The last known case was the Russian biathlete Olga Pyljowa at the 2006 Winter Olympics in Turin on February 16, 2006.

On August 8, 2008, the Russian athlete Viktor Burajew was tested for Carphedon with a positive A-sample. The B sample is still pending.

drug

In Germany and Austria there are currently no finished medicinal products with this active ingredient available.

In Russia the preparation is marketed under the name Phenotropil .

Stereochemistry

Carphedon contains a stereocenter and consists of two enantiomers. This is a racemate , a 1: 1 mixture of ( R ) - and ( S ) -form:

Enantiomers of carphedon
(R) -Carphedon Structural Formula V1.svg
CAS No .: 949925-07-9 		(S) -Carphedon Structural Formula V1.svg
CAS No .: 949925-08-0

Derivatives

  • E1R , (4 R , 5 S ) -5-methyl-4-phenylpiracetam, is a positive  allosteric modulator of  the  sigma-1 receptor , improves cognition and is effective against cholinergic dysfunction in mice without influencing locomotor activity. Pretreatment with E1R improved the stimulating effect of the σ 1 R agonist  PRE-084 and encouraged retention of passive avoidance. It reduced cognitive impairment induced by scopolamine . The cognitive ability enhancing effect of E1R is stronger than that of ( R ) -phenylpiracetam. Because E1R had no effect on locomotor functions, it was found to be free of potential motor side effects .
  • In Phenylpiracetamhydrazid , also known as Fonturacetamhydrazid which is amide group by a hydrazide replaced group. It was first introduced by Russian researchers in 1980 as part of a series of chemical substances studied as anticonvulsants . An ED 50 of 310 mg / kg was determined in an electric shock test.

Individual evidence

  1. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 1-pyrrolidineacetamide, 2-oxo-4-phenyl- in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 28, 2019, is reproduced from a self-classification by distributors .
  2. ↑ S. Kim, JH Park, SW Myung, DS Lho: Determination of carphedon in human urine by solid-phase microextraction using capillary gas chromatography with nitrogen-phosphorus detection . In: The Analyst . 124, No. 11, 1999, pp. 1559-1562. doi : 10.1039 / a906027h . PMID 10746314 .
  3. ↑ a b A. G. Malykh, MR Sadaie: Piracetam and Piracetam-Like Drugs . In: Drugs . 70, No. 3, 2010, pp. 287-312. doi : 10.2165 / 11319230-000000000-00000 . PMID 20166767 .
  4. ↑ L. Zvejniece, B. Svalbe, G. Veinberg, S. Grinberga, M. Vorona, I. Kalvinsh, M. Dambrova: Investigation into stereoselective pharmacological activity of phenotropil. . In: Basic & Clinical Pharmacology & Toxicology . 109, No. 5, 2011, pp. 407-12. doi : 10.1111 / j.1742-7843.2011.00742.x . PMID 21689376 .
  5. ^ AI Savchenko, NS Zakharova, IN Stepanov: The phenotropil treatment of the consequences of brain organic lesions . In: Zhurnal nevrologii i psikhiatrii imeni SS Korsakova . 105, No. 12, 2005, pp. 22-26. PMID 16447562 .
  6. ↑ a b Yu. Yu. Firstova, DA Abaimov, IG Kapitsa, TA Voronina, GI Kovalev: The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task . In: Neurochemical Journal . 28, No. 2, 2011, pp. 130-141. doi : 10.1134 / S1819712411020048 .
  7. ^ I. Bobkov, IS Morozov, OM Glozman, LN Nerobkova, LA Zhmurenko: Pharmacological characteristics of a new phenyl analog of piracetam - 4-phenylpiracetam . In: Biulleten 'eksperimental'noi biologii i meditsiny . 95, No. 4, 1983, pp. 50-53. PMID 6403074 .
  8. ↑ Tiurenkov IN, Bagmetov MN, Epishina VV: Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia . In: Eksp Klin Farmakol . 70, No. 2, 2007, pp. 24-29. PMID 17523446 .
  9. ↑ ABDA database (as of July 24, 2008) of DIMDI .
  10. ↑ Austria Codex (as of July 24, 2008).
  11. ↑ phenotropil.ru: ФЕНОТРОПИЛ ( Memento of the original from December 21, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (soot.) @1@ 2Template: Webachiv / IABot / www.phenotropil.ru
  12. ↑ E Vavers, L Zvejniece, G Veinberg, B Svalbe, I Domracheva, R Vilskersts, M Dambrova: Novel positive allosteric modulator of sigma-1 receptor . In: SpringerPlus . 4, 2015, p. P51. doi : 10.1186 / 2193-1801-4-S1-P51 . "The R-configuration enantiomers of methylphenylpiracetam are more active positive allosteric modulators of Sigma-1 receptor than S-configuration enantiomers."
  13. ↑ a b c d e L Zvejniece, E Vavers, B Svalbe, R Vilskersts, I Domracheva, M Vorona, G Veinberg, I Misane, I Stonans, I Kalvinsh, M Dambrova: The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors . In: British Journal of Pharmacology . 171, No. 3, 2014, pp. 761-71. doi : 10.1111 / bph.12506 . PMID 24490863 . PMC 3969087 (free full text).
  14. ↑ G Veinberg, M Vorona, L Zvejniece, R Vilskersts, E Vavers, E Liepinsh, H Kazoka, S Belyakov, A Mishnev, J Kuznecovs, S Vikainis, N Orlova, A Lebedev, Y Ponomaryov, M Dambrova: Synthesis and Biological Evaluation of 2- (5-methyl-4-phenyl-2-oxopyrrolidin-1-yl) -acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor . In: Bioorganic & Medicinal Chemistry . 21, No. 10, 2013, pp. 2764-71. doi : 10.1016 / j.bmc.2013.03.016 . PMID 23582449 .
  15. ↑ G Veinberg, E Vavers, N Orlova, J Kuznecovs, I Domracheva, M Vorona, L Zvejniece, M Dambrova: Stereochemistry of phenylpiracetam and its methyl derivative: improvement of the pharmacological profile . In: Chemistry of Heterocyclic Compounds . 51, No. 7, 2015, pp. 601-606. doi : 10.1007 / s10593-015-1747-9 . "In conclusion, the obtained data demonstrated that E1R is the most active memory enhancing enantiomer of the 5-methyl-substituted phenylpiracetam homolog, and its cognition enhancing activity is higher than that of (R) -phenylpiracetam."
  16. ↑ International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 63 . In: WHO Drug Information . 24, No. 1, 2010, p. 56. Retrieved November 26, 2015.
  17. ↑ a b O. M. Glozman, IS Morozov, LA Zhmurenko, VA Zagorevskii: Synthesis and anticonvulsive activity of 4-phenyl-2-pyrrolidinone-1-acetic acid amides . In: Khimiko-Farmatsevticheskii Zhurnal . 14, No. 11, 1980, pp. 43-48.

literature

  • Bobkov, Yu.G. et al. (1983): Pharmacological characteristics of 4-phenylpiracetam - A new phenyl analog of piracetam. In: Bulletin of Experimental Biology and Medicine. Vol. 95, No. 4, 464-467. doi : 10.1007 / BF00838859

Web links