Effect of YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT 2A receptor antagonistic activity, on a marble-burying behavior test as an obsessive-compulsive disorder model.
YM992 ((S)-2-[[(7-fluoroindan-4-yl)oxy]methyl]morpholine) monohydrochloride is a novel antidepressant with selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibition and 5-HT(2A) receptor antagonistic activity. The effects of YM992 and two selective 5-HT re-uptake inhibitors (SSRIs) were studied in a marble-burying behavior test as a model of an obsessive-compulsive disorder (OCD) in mice at doses of 5, 10 and 15 mg/kg, i.p. YM992 and fluoxetine significantly inhibited marble-burying behavior at a dose of 15 mg/kg (i.p.) without affecting spontaneous locomotor activities. Citalopram also significantly inhibited the behavior at doses of 5, 10 and 15 mg/kg (i.p.) without affecting spontaneous locomotor activities. These results suggest that YM992, as well as SSRIs, may exhibit anti-OCD activity in addition to an antidepressive effect in clinical use.
Takeuchi
Hiromi
H
Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan. takeuchi.hiromi@yamanouchi.co.jp
Yatsugi
Shin-ichi
S
Yamaguchi
Tokio
T
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000523:psychology; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000928:Antidepressive Agents; D015283:Citalopram; D005473:Fluoxetine; D009025:Morpholines; D044402:Receptor, Serotonin, 5-HT2A; D017367:Selective Serotonin Reuptake Inhibitors; C105748:lubazodone hydrochloride