Differences between the tolerance characteristics of two anticonvulsant benzodiazepines.
Clobazam (10 mg/kg) and clonazepam (0.25 mg/kg) were administered to mice twice daily by the intraperitoneal route. The development of tolerance to their anticonvulsant effect was compared using a slow intravenous infusion of pentylenetetrazole as the convulsant stimulus. Tolerance to clonazepam developed gradually throughout a 72 h study and did not become significant until the fifth dose. In contrast, tolerance to clobazam occurred extremely rapidly, after only one dose; it was manifested as a single step and no further significant change in protection was observed. Recovery from benzodiazepine tolerance was also studied and seen to occur rapidly with both these compounds; following cessation of dosing, protection was restored to initial levels within 36-48 h.
D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology*; D000078306:Clobazam; D002998:Clonazepam / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D013997:Time Factors
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D001569:Benzodiazepines; D000078306:Clobazam; D002998:Clonazepam; D010433:Pentylenetetrazole