Abstracts

Rationale: Prior studies have shown that cysteinyl-leukotriene (LT) production is increased during limbic seizures triggered by kainic acid. It is possible that LT and LT-R could be associated with mechanisms of seizure onset, and epileptogenesis. The aim of this study is to evaluate whether the CysLT1 receptor antagonist, pranlukast (PL), would suppress PTZ kindling, maximum electrical shock (MES) or pentylenetetrazol (PTZ) induced convulsive seizures. Methods: Rats aged 8 weeks were given two weeks of a CE-2 diet (Clea, Co., Ltd. Japan) that contained 0.6 w/w％ of pranlukast. The anticonvulsant effect was tested using MES, PTZ-induced convulsions, and PTZ kindling. PTZ induced convulsions were estimated according the scoring method of Becker ²⁾. MES was induced with 70V 3 sec electrical stimulation delivered from bilateral ear electrodes, and the duration was measured following the convulsion . PTZ-induced convulsions were induced with 45 mg i.p. of PTZ . PTZ (25mg/kg, i.p.) kindling was induced with repeated administered at 3 times per week, and during 20 min after each stimulation, PTZ convulsive stages were monitored at 15 sec intervals. For each experiment, control rats were given a diet of CE-2 but without PL under the same conditions light-dark, temperature and humidity. Statistical analysis was performed using with ANOVA by STATVIEW for WINDOWS ver 5.0. Results: Although there was slight suppression of PTZ kindling stage development, convulsive severity at each stimulation observed in the PL group was statistically less intense than that of CE-2 alone. Diet with pranlukast added suppressed both MES and PTZ-induced seizures when compared to control. Conclusions: Montelukast sodium, a leukotriene D(4) receptor antagonist markedly and in a dose dependent fashion suppressed the development of kindled seizures as well as pilocarpine induced spontaneous recurrent seizures. PL , a blocker of LT-R，suppressed convulsion induced by MES, PTZ and kindling. The mechanism, of suppression of 14-day PL diet of convulsions may be related to enhanced release of LT when rat brain is stimulated by MES or PTZ..