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 a ntagonist MK-801 0,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hy drogen maleate) as an anticonvulsant. This potent pharmacological effe ct of DTG distinguishes it from two other prototypic sigma ligands, ha loperidol and (+)-pentazocine, which are ineffective as anticonvulsant s. Pretreatment of animals with haloperidol failed to block the antico nvulsant effects of DTG. These data therefore document a novel anticon vulsant action of DTG in vivo by a mechanism that does not involve sig ma receptors.