Isoniazid-induced convulsions in rats: effects of Ro 15-1788 and beta-CCE

Dose-response curves for the convulsant effect of isoniazid were determined in male rats. The specific benzodiazepine antagonist Ro 15-1788, at doses from 20 to 100 mg/kg i.v. or at 300 mg/kg p.o., failed to produce any relevant shift of the isoniazid dose-response curves to the left (proconvulsant) or to the right (anticonvulsant). In contrast, the benzodiazepine receptor ligand ethyl-beta-carboline-3-carboxylate (beta-CCE) 10 mg/kg i.v. produced a clear-cut shift to the left of the isoniazid dose-response curve. Ro 15-1788 was inactive up to high p.o. or i.v. doses, versus convulsions induced by a low supraliminal dose of isoniazid, whereas beta-CCE had a significant proconvulsant effect beginning at 5 mg/kg i.v. This effect of beta-CCE was dose dependently antagonized by Ro 15-1788. In conclusion, in the present experimental conditions Ro 15-1788 showed no inverse agonistic properties at benzodiazepine receptors, in contrast to beta-CCE.