Comparative pharmacological activity of optical isomers of phenibut

Maija Dambrova, Liga Zvejniece, Edgars Liepinsh, Helena Cirule, Olga Zharkova, Grigory Veinberg, Ivars Kalvinsh

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Phenibut (3-phenyl-4-aminobutyric acid) is a GABA (γ-aminobutyric acid)-mimetic psychotropic drug which is clinically used in its racemic form. The aim of the present study was to compare the effects of racemic phenibut and its optical isomers in pharmacological tests and GABAB receptor binding studies. In pharmacological tests of locomotor activity, antidepressant and pain effects, S-phenibut was inactive in doses up to 500 mg/kg. In contrast, R-phenibut turned out to be two times more potent than racemic phenibut in most of the tests. In the forced swimming test, at a dose of 100 mg/kg only R-phenibut significantly decreased immobility time. Both R-phenibut and racemic phenibut showed analgesic activity in the tail-flick test with R-phenibut being slightly more active. An GABAB receptor-selective antagonist (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP35348) inhibited the antidepressant and antinociceptive effects of R-phenibut, as well as locomotor depressing activity of R-phenibut in open field test in vivo. The radioligand binding experiments using a selective GABAB receptor antagonist [3H]CGP54626 revealed that affinity constants for racemic phenibut, R-phenibut and reference GABA-mimetic baclofen were 177 ± 2, 92 ± 3, 6.0 ± 1 μM, respectively. We conclude that the pharmacological activity of racemic phenibut relies on R-phenibut and this correlates to the binding affinity of enantiomers of phenibut to the GABAB receptor.

Original languageEnglish
Pages (from-to)128-134
Number of pages7
JournalEuropean Journal of Pharmacology
Volume583
Issue number1
DOIs
Publication statusPublished - 31 Mar 2008
Externally publishedYes

Keywords

  • GABAB receptors
  • Optical isomer
  • Pharmacological activity
  • Phenibut

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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