A possible role of GABAergic mechanism in the convulsant action of RO5-4864

Santosh K. Rastogi, Maharaj K. Ticku

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The purpose of the present investigation was to determine the possible role of GABAergic mechanism in the convulsant action of RO5-4864. Benzodiazepines (BZ) and other agents which facilitate central GABAergic transmission delayed the onset of facial and forelimb clonus, whereas tonic hind limb extension was blocked in a dose-dependent manner. RO5-4864-induced convulsions were blocked by diazepam, clonazepam, pentobarbital, ethanol and amino-oxyacetic acid (AOAA). RO5-4864-induced convulsions were not blocked by the BZ antagonist RO15-1788. Specifically, RO15-1788 caused a decrease in the onset of severity component of tonic seizures, which tended to become generalized and precipitated in a tonic extension of the hindlimbs. Further, subconvulsive doses of a direct GABA receptor antagonist, bicuculline, enhanced the proconvulsant action of RO5-4864, indicating thereby a potential antagonism of the central GABAergic transmission. These observations strongly suggest that RO5-4864 probably elicits convulsions by selective impairment of the GABAergic transmission.

Original languageEnglish (US)
Pages (from-to)285-288
Number of pages4
JournalPharmacology, Biochemistry and Behavior
Volume23
Issue number2
DOIs
StatePublished - Aug 1985

Keywords

  • Barbiturates
  • Benzodiazepines
  • Convulsants
  • GABAergic transmission
  • Picrotoxin site
  • Receptor interactions
  • RO5-4864

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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