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) greater than dextrorphan greater than or equal to 1-(1-phenylcyclohexyl)piperidine hydrochloride (PCP) greater than dextromethorphan greater than (+)-pentazocine, upon microinjection into the prepiriform cortex, was highly correlated (r = 0.971; P less than 0.01) with their respective 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.
Roth
J E
JE
College of Pharmacy, Oregon State University, Corvallis 97331.
Zhang
G
G
Murray
T F
TF
Franklin
P H
PH
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D003915:Dextromethorphan / Q000494:pharmacology; D003917:Dextrorphan / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009294:Narcotics / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D013237:Stereoisomerism
D000927:Anticonvulsants; D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D003917:Dextrorphan; D016291:Dizocilpine Maleate; D003915:Dextromethorphan; D010622:Phencyclidine; D010423:Pentazocine; D001640:Bicuculline