Insulin impairs the anticonvulsive activity of carbamazepine against maximal electroshock-induced seizures in mice
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In view of the data indicating that insulin can modify penetration of some drugs across cell membranes and tissue barriers, particularly the blood-brain barrier, the aim of the present study was to evaluate the effect of insulin on both the anticonvulsant activity and the brain concentration of carbamazepine in mice suffering from seizures induced by maximal electroshock. The antiepileptic drug was administered per os in single doses either alone or in combination with insulin given as single intraperitoneal injections. To assess the anticonvulsant activity of carbamazepine the ED50 values were calculated. The results indicate that insulin given in doses up to 2 units/kg did not affect the convulsive threshold, whereas insulin applied at 2 units/kg led to a significant reduction in the anticonvulsant activity of carbamazepine, as judged by an increase in the ED50 value from 16.2 to 41.3 mg/kg. This effect was accompanied by the marked reduction in both the brain and blood concentrations of the drug. It is likely, therefore, that the inhibitory activity of insulin on the anticonvulsive function of carbamazepine is related not only to the effect of the former on the blood-brain transport of the latter, but also to insulin-induced modulation of the serum concentration of the drug.
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M. Alaraj, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawinski St., 02-106 Warsaw, Poland