Pharmacological activities of clobazam and diazepam in the rat: relation to drug brain levels.
Brain distribution and various pharmacological effects of clobazam and diazepam were studied in rats. When given at 10 mg/kg i.p. the compounds reached peak brain levels 15 min after injection, and showed similar half lives. At peak time brain levels were proportional to the dose administered. Very little of the N-desmethylmetabolite of each compound was found in the brain. Clobazam was less effective than diazepam in protecting rats from pentetrazol convulsions. Disrupting rota-rod performance and increasing punished responses in a "conflict" test, the relative potencies ranging from 4 to 8 in the various tests. The results are discussed in relation to the importance of animal species selection for predicting favourable therapeutic effects in humans.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D000927:Anticonvulsants; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D000078306:Clobazam; D003220:Conflict, Psychological; D003975:Diazepam / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D007700:Kinetics; D004856:Postural Balance; D051381:Rats
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D001569:Benzodiazepines; D000078306:Clobazam; D003975:Diazepam