The sigma receptor ligand 1,3-di(2-tolyl)guanidine is anticonvulsant in the rat prepiriform cortex.
Unilateral focal injection of 1,3-di(2-tolyl)guanidine (DTG) caused a dose-dependent and potent (ED50 = 5.25 nmol, 95% confidence limits 1.1 to 25.0 nmol) suppression of generalized motor seizures induced by (-)-bicuculline methiodide in the rat prepiriform cortex. These findings indicate that DTG is equipotent to the noncompetitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate) as an anticonvulsant. This potent pharmacological effect of DTG distinguishes it from two other prototypic sigma ligands, haloperidol and (+)-pentazocine, which are ineffective as anticonvulsants. Pretreatment of animals with haloperidol failed to block the anticonvulsant effects of DTG. These data therefore document a novel anticonvulsant action of DTG in vivo by a mechanism that does not involve sigma receptors.
Roth
J E
JE
College of Pharmacy, Oregon State University, Corvallis 97331.
Franklin
P H
PH
Murray
T F
TF
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity; D001921:Brain / Q000187:drug effects; D004347:Drug Interactions; D006146:Guanidines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D006146:Guanidines; D017480:Receptors, sigma; C017069:bicuculline methiodide; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D001640:Bicuculline