Abstract
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 σ 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 σ receptors.