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.