Effects of zometapine, a structurally novel antidepressant, in an animal model of depression

Zometapine, a pyrazolodiazepine, bears a close structural resemblance to benzodiazepines. It possesses an unusual pharmacological profile, and is active in some, but not all, tests of antidepressant activity. In clinical tests it appears to be an extremely effective pharmacotherapeutic agent, and may represent a new class of antidepressant. Because the preclinical profile of zometapine is unusual, we examined its effects in a behavioral test of antidepressant potential. Following three weeks of treatment, the drug selectively reversed a behavioral depression following chronic stress. Drug-induced reversal was seen only in rats activated by acute noise exposure, and was dose related. Reversal was confirmed by a second measure, defecation, and partially confirmed by the normalization of an elevated basal corticosterone response.