2-Methyl-6-phenylethynyl-pyridine (MPEP), a non-competitive mGluR5 antagonist, differentially affects the anticonvulsant activity of four conventional antiepileptic drugs against amygdala-kindled seizures in rats.

2-Methyl-6-phenylethynyl-pyridine (MPEP), a selective noncompetitive mGluR5 antagonist, influences the action of conventional antiepileptic drugs in amygdala-kindled seizures in rats. MPEP alone (up to 40 mg/kg) did not affect any seizure parameter. Moreover, the common treatment of MPEP with either carbamazepine or phenytoin (administered at subeffective doses) did not result in any anticonvulsant action in kindled rats. However, when combined with subprotective doses of valproate or phenobarbital, MPEP significantly shortened seizure and afterdischarge durations. Importantly, combinations of MPEP with the two antiepileptics did not have the adverse effects of impaired motor performance or long-term memory in rats. Our data indicate that MPEP may positively interact with some conventional antiepileptic drugs in the amygdala-kindling model of complex partial seizures.