Interactions of the imidazodiazepine Ro 15-4513 with chemical convulsants

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Abstract
1 The proconvulsant effects of the imidazodiazepine Ro 15–4513, were investigated in mice by use of intravenous infusion of a variety of convulsant drugs. 2 Dose-response and time course studies of Ro 15–4513 against γ-aminobutyric acid (GABA) antagonists were performed. On the basis of these studies a maximally effective dose of 5 mg kg−1 was administered 5 min before the determination of seizure thresholds in subsequent experiments. 3 Ro 15–4513 (5 mg kg−1) significantly lowered seizure thresholds to pentylenetetrazole, bicuculline and the convulsant benzodiazepine Ro 5–3663, but failed to alter seizure thresholds to picrotoxin, strychnine, caffeine and quipazine. 4 Ro 15–4513 significantly raised seizure threshold to the benzodiazepine receptor inverse agonist methyl 6,7-dimethoxy-4 ethyl-β-carboline-3-carboxylate (DMCM). 5 These results are discussed in relation to other studies investigating the proconvulsant and alcohol-antagonizing effects of Ro 15–4513.