Stiripentol in acute/chronic efficacy tests in monkey model

Abstract

Acute and chronic efficacy tests of stiripentol (4,4-dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol) were conducted in alumina-gel rhesus monkeys. In the acute study (n = 6), discrete serial seizures precipitated by 150 mg/kg of 4-deoxypyridoxine hydrochloride were challenged by intravenous administration of stiripentol and the data compared with those obtained with valproate similarly tested in other monkeys (reported here) and with those from four other standard anticonvulsants (phenytoin, carbamazepine, phenobarbital, and diazepam--data published previously). In the acute challenge (Study 1), stiripentol performed comparably to valproate by delaying the onset of seizures but not eliminating them as did the other four drugs. In two separate chronic studies (at different doses, n = 6 each), stiripentol was given every 4 h by gastric catheter for 4 weeks, preceded and followed by 4 weeks of baseline. In these studies, stiripentol significantly reduced EEG interictal spike rates at mean plasma concentrations from 20 to 27 micrograms/ml in Study 2 and 11 to 14 micrograms/ml in Study 3. From these results, and those evinced in other studies, it appears that stiripentol should be evaluated for absence epilepsy and possible synergistic effects in polytherapy.