AHR-9377, a new antidepressant agent

AHR-9377 is a novel chemical structure with potential antidepressant activity. It was more potent than imipramine in mice, and equipotent with imipramine in rats in blocking tetrabenazine ptosis. Yohimbine toxicity in mice was potentiated by AHR-9377 in doses less than those of imipramine. The compound had no CNS stimulant properties as judged by behavioral observations and spontaneous motor activity determinations in rats and by its lack of effect on rectal temperature of normothermic rats. In rats made hyperthermic with d-amphetamine, however, AHR-9377, like imipramine, prolonged the hyperthermic effect. Contractions of the cat nictitating membrane that were induced by norepinephrine were potentiated by AHR-9377. Unlike iproniazid, AHR-9377 had no monoamine oxidase-inhibiting activity. Electroencephalographic analyses indicated no slowing of cortical activity and no spindle-type waves in cats after AHR-9377 administration. These data suggest that AHR-9377 is a potential antidepressant agent without sedative activity.