Interaction of loreclezole with conventional antiepileptic drugs in amygdala-kindled rats

Loreclezole (5 mg/kg) exerted a significant protective action against amygdala-kindled rats, reducing both seizure and afterdischarge (AD) durations. Subsequently, the effect of combinations of loreclezole (at non-effective doses) with some conventional antiepileptics (at their subtherapeutic doses) was evaluated. The co-administration of loreclezole (2.5 mg/kg) with phenobarbital (15 mg/kg) or diphenylhydantoin (2.5 mg/kg) did not influence any seizure correlates. However, the combined treatment of loreclezole (2.5 mg/kg) with valproate (50 mg/kg) significantly reduced the afterdischarge duration. Its combination with carbamazepine (15 mg/kg) reduced the seizure severity (SSv) and both seizure and afterdischarge durations. Also, the concomitant treatment of loreclezole (2.5 mg/kg) with clonazepam (0.05 mg/kg) resulted in a significant decrease of seizure and afterdischarge durations. Loreclezole did not affect the free plasma concentrations of valproate or clonazepam, so a pharmacokinetic interaction is not probable. Although, loreclezole significantly increased the free plasma concentration of carbamazepine. The results point to the potential therapeutic effects of combinations of loreclezole with valproate or clonazepam. (C) 2003 Elsevier B.V./ECNP. All rights reserved.