Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate receptor antagonist, in a marble-burying behavior test.
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.
Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Toshiharu
T
Shimazaki
Michihiko
M
Iijima
Shigeyuki
S
Chaki
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D003998:Dicarboxylic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000523:psychology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology
C483757:2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid; D014151:Anti-Anxiety Agents; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2