Characterization of convulsions induced by methyl beta-carboline-3-carboxylate in mice.
The convulsive properties of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in mice. When injected subcutaneously at a dose of 10 mg/kg beta-CCM induced convulsions in 75% of the mice with a median latency of 2.12 +/- 0.25 min. The CD50 was determined to be about 5 mg/kg. Electroencephalographic recordings showed that convulsions were brief (10 s), of cortical origin and propagating rapidly to the hippocampus. EEG alterations induced by low doses of beta-CCM lasted up to 1 h. The convulsive effect of beta-CCM was compared to that of PTZ. PTZ-induced convulsions occurred with a longer latency (9.26 +/- 1.33 min). beta-CCM and PTZ could act synergistically when injected in non-convulsive doses. When beta-CCM was injected 2-30 min before pentylenetetrazol (PTZ) there was a clear potentiation of the convulsive effect of PTZ. The convulsions induced by beta-CCM were blocked by diazepam (DZ) and by Ro 15-1788. In addition, beta-CCM reversed the sedative effect of a high dose of DZ for more than 30 min. Our results confirm that beta-CCM acts through the BZ receptor and indicate that the effects induced by a single dose of beta-CCM last more than 30 min.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003292:Convulsants / Q000037:antagonists & inhibitors; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography; D005442:Flumazenil; D006993:Hypnotics and Sedatives; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D013997:Time Factors
D001570:Benzodiazepinones; D002243:Carbolines; D003292:Convulsants; D006993:Hypnotics and Sedatives; D007211:Indoles; D005442:Flumazenil; C036150:beta-carboline-3-carboxylic acid methyl ester; D003975:Diazepam; D010433:Pentylenetetrazole