Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate receptor antagonist, in a marble-burying behavior test.

Abstract

Glutamatergic abnormalities are involved in several psychiatric disorders. Clinical evidence demonstrates altered glutamatergic neurotransmission in patients suffering from obsessive-compulsive disorder. MGS0039, (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid, is a novel group II metabotropic glutamate (mGlu) receptor antagonist. We examined MGS0039's potential anti-obsessive-compulsive disorder activity, using the marble-burying behavior test as a model of obsessive-compulsive disorder. MGS0039 as well as LY341495 ((2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'-carboxycycloprolyl)glycine), another group II mGlu receptor antagonist, inhibited marble-burying behavior. We also demonstrated that this effect was significantly attenuated by a group II mGlu receptor agonist. This data indicates that group II mGlu receptor antagonists may exert anti-obsessive-compulsive disorder effects in clinical use.

• Authors: Toshiharu Shimazaki, Michihiko Iijima, Shigeyuki Chaki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 501 Issue 1-3 Pg. 121-5 (Oct 06 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15464070 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid
• Anti-Anxiety Agents
• Bridged Bicyclo Compounds
• Dicarboxylic Acids
• Excitatory Amino Acid Antagonists
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor 2

Topics

• Animals
• Anti-Anxiety Agents (pharmacology, therapeutic use)
• Behavior, Animal (drug effects, physiology)
• Bridged Bicyclo Compounds (pharmacology, therapeutic use)
• Dicarboxylic Acids (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Antagonists (pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred ICR
• Obsessive-Compulsive Disorder (drug therapy, psychology)
• Receptors, Metabotropic Glutamate (antagonists & inhibitors, physiology)