ANTICONVULSANT EFFECTS BY COMBINED TREATMENT WITH A GLYCINE(B) RECEPTOR ANTAGONIST AND A POLYAMINE SITE ANTAGONIST IN AMYGDALA-KINDLED RATS

Antagonists of binding sites within the NMDA receptor complex, i.e., L -701,324 loro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)quinolone), a brain pe netrating glycine, receptor antagonist, and ifenprodil, a polyamine si te antagonist, were tested for anticonvulsant properties in fully amyg dala-kindled rats, a model of limbic epilepsy. Both drugs were not abl e to significantly change seizure parameters (focal afterdischarge thr eshold, seizure severity, and duration of seizure and afterdischarges) , when administered intraperitoneally up to doses which produced sever e motor impairment. However, the combination of 10 mg/kg ifenprodil an d 5 mg/kg L-701,324 had a pronounced anticonvulsant effect on afterdis charge threshold and seizure severity without concomitant increase of adverse effects. These findings support the hypothesis that drugs acti ng only at one site of the NMDA receptor complex are ineffective, whil e combinations of such drugs may synergistically act to suppress limbi c seizures, thus providing an adequate strategy for the treatment of t his type of refractory epilepsy. (C) 1997 Elsevier Science B.V.