Keisuke Ishizawa, Zhong Chen, Chihiro Okuma, Yukio Sugimoto, Yoko Fujii
and Chiaki Kamei*
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama
University, Okayama 700Ð8530, Japan
*To whom correspondence should be addressed.
Abstract: The effects of GABAmimetic drugs on inhibition of amygdaloid
kindled seizures induced by clobenpropit were investigated to clarify the
relationship between histaminergic and GABAergic systems in seizures. I.p.
injection of clobenpropit caused doseÐdependent inhibition of amygdaloid
kindled seizures. GABAmimetic drugs such as diazepam, sodium valproate and
muscimol also inhibited amygdaloid kindled seizures in a doseÐdependent
manner. Diazepam at doses of 0.2 and 0.5 mg/kg, which showed no significant
effect on amygdaloid kindled seizures when used separately, significantly
potentiated the effect of clobenpropit. Similar findings were observed with
sodium valproate and muscimol at doses of 100 mg/kg and 5 ng, respectively,
although neither showed any significant effects when administered separately.
Bicuculline caused significant antagonism of the inhibition of amygdaloid
kindled seizures induced by clobenpropit, while the effect of diazepam was
not antagonized by diphenhydramine. These results suggested that inhibition
of amygdaloid kindled seizures induced by histamine is closely associated
with the actions of GABA.
Keywords: Amygdaloid kindling, Clobenpropit, Diazepam, Histamine, GABA