title: Differences between the tolerance characteristics of two anticonvulsant benzodiazepines in the amygdaloid-kindled rat.
abstract: The characteristics of the development of tolerance to the anticonvulsant effects of chronic treatment by dipotassium clorazepate and diazepam using amygdaloid-kindled rats were investigated. Dipotassium clorazepate (5 mg/kg) or diazepam (5 mg/kg) were intraperitoneally administered for 10 consecutive days. Tolerance to the anticonvulsant effect of dipotassium clorazepate developed in seizure stage on day 6, after-discharge duration on day 7 and seizure latency on day 4. In contrast, tolerance to the effects of diazepam developed more rapidly in seizure stage on day 4, after-discharge duration on day 4 and seizure latency on day 3. Thus tolerance to the anticonvulsive effect of dipotassium clorazepate developed relatively slower than that to diazepam. All rats had stage 5 convulsions 24 hr after cessation of the administration of dipotassium clorazepate and diazepam. Concomitant determinations of plasma concentrations of the main metabolite of dipotassium clorazepate and diazepam, desmethyldiazepam, showed no statistical difference during treatment, suggesting that the developed tolerance was not metabolic but functional.
authors.affiliation: Department of Psychiatry, Kikuchi National Hospital, Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Amano
authors.forename: S
authors.initials: S
authors.lastname: Katsuragi
authors.forename: J
authors.initials: J
authors.lastname: Takamatsu
authors.forename: A
authors.initials: A
authors.lastname: Ogata
authors.forename: C
authors.initials: C
authors.lastname: Miyazaki
authors.forename: M
authors.initials: M
authors.lastname: Deshimaru
authors.forename: T
authors.initials: T
authors.lastname: Miyakawa
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003009:Clorazepate Dipotassium / Q000008:administration & dosage / Q000494:pharmacology*; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004361:Drug Tolerance; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D003009:Clorazepate Dipotassium; D003975:Diazepam