Increased Mortality of Kainic Acid by Pretreatment with Nicardipine, a Calcium Channel Blocker in Rats

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Ca2+ channel blockers from two different chemical classes, nifedipine and varapamil, were compared in rats for their ability to inhibit the wet-dog shakes behavior and limbic seizures induced by kainic acid which binds to a subtype of glutamate receptors in the brain. Pretreatment for 30 minutes with nicardipine or verapamil suppressed slightly kainic acid-induced wet-dog shakes independent of the dose 1-4mg/kg. In the rats treated with 5mg/kg of nicardipine or verapamil, however, the frequency of wet-dog shakes decreased to 50-60% of controls. In contrast, nicardipine accelerated the onset time and frequency of limbic seizures, resulting in increased mortality by kainic acid in the dose-dependent manner. Occurrence of limbic seizures in verapamil-treated rats was similar to that in the controls and the mortality in this group was smaller than in the nicardipine-treated group. Pretreatment with diazepam alone prevented the kainic acid-induced limbic seizures. However, in the rats pretreated with diazepam and nicardipine simultaneously, anticonvulsive effect of diazepam was not shown and the mortality in this group was the similar to that in the nicardipine pretreated group. Both nicardipine and verapamil did not enhance the picrotoxin-induced convulsions. The mechanism of the apparent enhancement of the mortality of kainic acid by even low doses of nicardipine is not clear. This might be, at least in part, correlated with their different mechanism of channel blocking action.
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Increased Mortality of Kainic Acid by Pretreatment with Nicardipine, a Calcium Channel Blocker in Rats

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