Investigation into Stereoselective Pharmacological Activity of Phenotropil

Liga Zvejniece, Baiba Svalbe, Grigory Veinberg, Solveiga Grinberga, Maksims Vorona, Ivars Kalvinsh, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)
18 Downloads (Pure)


Phenotropil [N-carbamoylmethyl-4-aryl-2-pyrrolidone (2-(2-oxo-4-phenyl-pyrrolidin-1-yl) acetamide; carphedon)] is clinically used in its racemic form as a nootropic drug that improves physical condition and cognition. The aim of this study was to compare the stereoselective pharmacological activity of R- and S-enantiomers of phenotropil in different behavioural tests. Racemic phenotropil and its enantiomers were tested for locomotor, antidepressant and memory-improving activity and influence on the central nervous system (CNS) using general pharmacological tests in mice. After a single administration, the amount of compound in brain tissue extracts was determined using an ultra performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method in a positive ion electrospray mode. In the open-field test, a significant increase in locomotor activity was observed after a single administration of R-phenotropil at doses of 10 and 50mg/kg and S-phenotropil at a dose of 50mg/kg. In the forced swim test, R-phenotropil induced an antidepressant effect at doses of 100 and 50mg/kg, and S-phenotropil was active at a dose of 100mg/kg. R-phenotropil significantly enhanced memory function in a passive avoidance response test at a dose of 1 mg/kg; the S-enantiomer did not show any activity in this test. However, the concentrations of R- and S-phenotropils in brain tissue were similar. In conclusion, the antidepressant and increased locomotor activity relies on both R- and S-phenotropils, but the memory-improving activity is only characteristic of R-phenotropil. These results may be important for the clinical use of optically pure isomers of phenotropil.

Original languageEnglish
Pages (from-to)407-412
Number of pages6
JournalBasic and Clinical Pharmacology and Toxicology
Issue number5
Publication statusPublished - Nov 2011

Field of Science*

  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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