The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Aug 1991
Kindling as a model of drug-resistant partial epilepsy: selection of phenytoin-resistant and nonresistant rats.
Complex partial seizures comprise the major uncontrolled seizure type in adult patients with epilepsy. Any improvement of our understanding of the mechanisms through which these seizures are often refractory to antiepileptic drugs is therefore of considerable importance. By examining the effects of the anti-epileptic drug phenytoin in a large group of kindled rats, a widely used model of complex partial seizures, animals with different sensitivity to this drug were selected. ⋯ In contrast to phenytoin, carbamazepine induced increases in focal seizure threshold in all kindled rats. Duration of seizures and afterdischarges were significantly reduced by carbamazepine in phenytoin responders, but not in nonresponders, although plasma levels of carbamazepine were the same in both groups. The difference in response of kindled rats to phenytoin was restricted to kindled seizures, because phenytoin induced the same anticonvulsant effect on the threshold for generalized tonic electroconvulsions (determined via transauricular electrodes) in both groups of kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS)