Levonantradol Potentiates the Anticonvulsant Effects of Diazepam and Valproic Acid in the Kindling Model of Epilepsy

Abstract

The anticonvulsant effects of the cannabinoid derivative levonantradol and its ability to potentiate the anticonvulsant effects of diazepam and valproic acid were studied in rats with previously established amygdala‐kindled seizures. Levonantradol administered in doses of 100 to 400 μg/kg did not block any components of the motor seizure. However, levonantradol did increase the latency of appearance of fully kindled seizures at the 400 μg/kg dose. Administration of diazepam at doses of 1 or 2 mg/kg or valproic acid at doses of 100 or 200 mg/kg produced seizure control as measured by a reduction in motor components of the seizure or a reduction in afterdischarge length or both. The anticonvulsant effects of diazepam and valproic acid were potentiated by administration of 100 μg/kg levonantradol without apparent increases in sedation. Although the mechanism underlying this potentiation of the antiepileptic effects of valproic acid and diazepam remains unknown, levonantradol may have potential as adjunctive therapy in the treatment of complex partial seizures.