Tolerance to the anticonvulsant effect of clorazepate and clonazepam in mice.
The rate of development of tolerance to the benzodiazepines clorazepate and clonazepam against pentetrazole-induced seizures in mice was compared. Treatment with clorazepate (0.1% solution as drinking water) for 21 days led to tolerance beginning at day 7. When mice were treated with clonazepam (0.5 mg/kg twice daily intraperitoneally), tolerance was evident already at the fourth day of treatment. Twenty-four hours after cessation of treatment the seizure threshold was significantly decreased after treatment with both drugs. Clorazepate, a prodrug of the main metabolite of diazepam, desmethyldiazepam, regards further interest for anticonvulsant therapy because of a relatively slow onset of tolerance.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002998:Clonazepam / Q000494:pharmacology*; D003009:Clorazepate Dipotassium / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D002998:Clonazepam; D003009:Clorazepate Dipotassium; D010433:Pentylenetetrazole