Activity of antihistamines in laboratory antidepressant tests

A series of antihistamines with widely differing chemical structures and pharmacological profiles have been compared to the standard antidepressants, imipramine and amitriptyline, in four laboratory antidepressant tests. Dexchlorpheniramine and tripelennamine are examples of antihistamines which were effective antagonists of tetrabenazine ptosis in mice, mouse-killing behavior in rats, and reserpine hypothermia in both species. Other antihistamines such as cyproheptadine, pyrilamine and promethazine were ineffective in these tests. The effectiveness of dexchlorpheniramine and tripelennamine in these procedures was equal to or greater than that of imipramine or amitriplyline. Potentiation of methamphetamine-induced excitation differed from other antidepressant tests because amitriplyline was ineffective, whereas promethazine, ineffective in other antidepressant tests, was a potent potentiator of methamphetamine.

After screening a series of nineteen clinically effective antihistamines for ability to prevent tetrabenazine-induced ptosis, it was found that all antihisiamines tested which are structurally related to pheniramine (alkylamine type) were effective tetrabenazine antagonists. Structural modifications of chlorpheniramine which cause severe reductions in antihistamine potency, did not affect anti-tetrabenazine activity. It is concluded that there is no correlation between antihistamine activity and activity in the aforementioned selected tests for antidepressant activity.