Interactions of the imidazodiazepine Ro 15-4513 with chemical convulsants.
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 gamma-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-beta-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.
Lister
R G
RG
Laboratory of Clinical Studies, DICBR, NIAAA, Bethesda, MD 20892.
Nutt
D J
DJ
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000037:antagonists & inhibitors; D001640:Bicuculline / Q000037:antagonists & inhibitors; D002243:Carbolines / Q000037:antagonists & inhibitors; D003292:Convulsants / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D010852:Picrotoxin / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D001386:Azides; D001569:Benzodiazepines; D001570:Benzodiazepinones; D001640:Bicuculline; D002243:Carbolines; D003292:Convulsants; D010433:Pentylenetetrazole; D010852:Picrotoxin; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; C022193:Ro 5-3663; C042957:Ro 15-4513