The σ receptor ligand 1,3-di(2-tolyl)guanidine is anticonvulsant in the rat prepiriform cortex

Jane E. Roth, Paul H. Franklin, Thomas F. Murray

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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.

Original languageEnglish
Pages (from-to)327-331
Number of pages5
JournalEuropean Journal of Pharmacology
Volume236
Issue number2
DOIs
Publication statusPublished - May 19 1993
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Pharmacology

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