Behavioral effects of HT-90B, a putative novel anxiolytic agent with potent antidepressive activity.
1. HT-90B,((-)-N-[2-(8-methyl-1,4-benzodioxane-2-ylmethyl)am in o]ethyl]tricyclo[3,3,1,1(3,7)] decane-1-carboxamide), is a novel serotonin 5-HT(1A) full agonist with serotonin 5-HT(2) antagonistic action. 2. In a water licking conflict test, HT-90B (3-30 mg/kg, po) was more effective than buspirone in abolishing response suppression. 3. In a forced swim test, HT-90B (3-30 mg/kg, po) reduced the duration of immobility after a single oral dose, which contrasts with the requirement of multiple doses for desipramine (as a standard antidepressant) to produce the effect. 4. These two behavioral effects of HT-90B (20 mg/kg,po) were still evident even 4 hr after oral administration. And no tolerance was observed for these behavioral effects after repeated oral administration (10 mg/kg, b.i.d., 2 weeks). 5. HT-90B hardly produced any diazepam- or buspirone-like side effects. 6. In conclusion, it is suggested HT-90B is a potent anti-depressive anxiolytic with minimal side effects.
Inagawa
K
K
Department of Pharmacology, Fuji-Gotemba Research Labs., Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Tameda
C
C
Uchida
H
H
Miyauchi
T
T
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology
D000928:Antidepressive Agents; C098902:HT 90B; D012702:Serotonin Antagonists; D000218:Adamantane