Differences in the development of tolerance to two anticonvulsant benzodiazepines in the amygdaloid kindled rat

Author:

Young N A1,Lewis S J1,Harris Q L Gg1,Jarrott B1,Vajda F J E1

Affiliation:

1. University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Austin Hospital, Heidelberg, Victoria 3084, Australia

Abstract

Abstract The effects of chronic treatment with two benzodiazepines were studied on kindled amygdaloid seizures in rats. Clobazam (4 mg kg−1), clonazepam (0.3 mg kg−1) or vehicle (1 mL kg−1) was administered, by intraperitoneal injection, to fully kindled rats twice daily for nineteen days. Each rat was electrically stimulated 30 min after the morning dose on alternate days of treatment. Tolerance developed rapidly to the anticonvulsant effects of clobazam after only three days of treatment, following which only a small residual protection was maintained. Tolerance to clonazepam developed gradually over the course of the experiment, although this effect was relatively minor.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference18 articles.

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2. Benzodiazepines in the treatment of epilepsy. A review;Browne;Epilepsia,1973

3. Pharmacological activities of clobazam and diazepam in the rat: relation to drug brain levels;Caccia;Arch. Int. Pharmacodyn.,1980

4. Potential relevance of kindling to human partial epilepsy;Engel,1986

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