Modulators of metabotropic glutamate receptors microinfused into perirhinal cortex: anticonvulsant effects in rats challenged with soman.

Abstract

Examination of critical subreceptors in the seizure controlling perirhinal cortex has revealed that microinfusion of ionotropic glutamatergic antagonists can exert anticonvulsant efficacy against soman-induced seizures. The purpose of the present study was to investigate whether modulators of metabotropic glutamate (mGlu) receptors may ensure anticonvulsant effects when microinfused into the perirhinal cortex. The results showed that the mGlu5 receptor antagonist MPEP hydrochloride (2-Methyl-6-(phenylethynyl)pyridine hydrochloride) and the mGlu2/3 receptor agonist DCG-IV ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine) caused full protection against seizures or increased latency to onset of seizures, whereas the mGlu1 receptor antagonist LY367385 ((S)-(+)-alpha-Amino-4-carboxy-2-methylbenzeneacetic acid) did not produce anticonvulsant efficacy in response to systemically administered soman (1.3 x LD(50)). Low doses of the above modulators had no anticonvulsant effects, whereas too high dose of MPEP resulted in proconvulsant effects. The results suggest that the perirhinal cortex is a likely site of cholinergic recruitment of glutamatergic hyperactivity after exposure to a convulsant dose of soman. Modulators of mGlu receptors may represent an alternative or supplement to ionotropic glutamate antagonists as anticonvulsants against nerve agent-evoked seizures.

• Authors: Trond Myhrer, Siri Enger, Pål Aas
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 636 Issue 1-3 Pg. 82-7 (Jun 25 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20347777 (Publication Type: Journal Article)
• Copyright: (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Benzoates
• Cyclopropanes
• Pyridines
• Receptors, Metabotropic Glutamate
• alpha-methyl-4-carboxyphenylglycine
• 2-(2,3-dicarboxycyclopropyl)glycine
• 6-methyl-2-(phenylethynyl)pyridine
• Soman
• Glycine

Topics

• Animals
• Anticonvulsants (administration & dosage, pharmacology)
• Benzoates (administration & dosage, pharmacology)
• Cyclopropanes (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Glycine (administration & dosage, analogs & derivatives, pharmacology)
• Infusion Pumps
• Male
• Microinjections
• Pyridines (administration & dosage, pharmacology)
• Rats
• Rats, Wistar
• Receptors, Metabotropic Glutamate (agonists, antagonists & inhibitors, metabolism)
• Seizures (chemically induced, prevention & control)
• Soman (toxicity)
• Temporal Lobe (drug effects, metabolism, pathology)
• Time Factors