Modification of the anticonvulsant efficacy of diazepam by Ro-15-1788 in the kindled amygdaloid seizure model

Timothy E Albertson, J. F. Bowyer, M. G. Paule

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

The effects of various doses of diazepam and the new central benzodiazepine antagonist Ro-15-1788 were investigated in fully amygdaloid kindled rats. Diazepam had a pronounced dose-dependent anticonvulsant effect in this model. Ro-15-1788 dose-dependently reduced the behavioral ranks of the elicited kindled seizures to a maximum of 60% of control without consistently modifying the afterdischarge duration. No prestimulation convulsant effects were seen with Ro-15-1788. When 2 mg/kg i.p. of Ro-15-1788 was given after various doses of diazepam, the prestimulation sedation and ataxia caused by the high dose of diazepam (2 mg/kg i.p.) was reversed. The anticonvulsant effects of diazepam (0.5-2.0 mg/kg) were attenuated by treatment with 2 mg/kg Ro-15-1788. At the low dose of diazepam (0.25 mg/kg), increased reduction of behavioral rank and afterdischarge duration was seen after the 2 mg/kg dose of Ro-15-1788. Thus, Ro-15-1788 appears not to have proconvulsant properties in the kindled amygdaloid seizure model. Further, Ro-15-1788 appears to have some anticonvulsant properties of its own. Mixed agonist and antagonist effects were seen with Ro-15-1788 when given after various doses of diazepam in this model.

Original languageEnglish (US)
Pages (from-to)1597-1601
Number of pages5
JournalLife Sciences
Volume31
Issue number15
DOIs
StatePublished - Oct 11 1982

ASJC Scopus subject areas

  • Pharmacology

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