Dextrorotatory opioids and phencyclidine exert anticonvulsant action in prepiriform cortex

We have investigated the ability of an array of putative noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists to suppress convulsions induced by a unilateral, focal injection of (-)-bicuculline methiodide (118 pmol) into the rat prepiriform cortex. The anticonvulsant potency of these compounds, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801)>dextrorphan ≥ 1-(1-phenylcyclohexyl)piperidine hydrochloride (PCP)>dextromethorphan > (+)-pentazocine, upon microinjection into the prepiriform cortex, was highly correlated (r = 0.971; P <0.01) with their respectiv affinities for the [³H]dextrorphan-labelled NMDA receptors in rat forebrain membranes. These results suggest that noncompetitive antagonism of NMDA receptors underlies the anticonvulsant action of these compounds.