Effects of antihistaminic drugs in tests for antidepressant action

Antihistaminics of various chemical structures: chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, and thenalidine were investigated for the action in tests for antidepressant drugs. The antihistaminics did not affect significantly the spontaneous locomotor activity of rats. Most of them (chloropyramine, chlorpheniramine, diphenhydramine, promethazine and thenalidine) increased amphetamine hypermotility but chlorcyclizine significantly inhibited, and clemastine and mepyramine did not affect it. In mice, chlorcyclizine, mepyramine and promethazine inhibited amphetamine hypermotility, while others antihistaminics were without effect. L-DOPA-induced hypermotility in mice was inhibited by all compounds tested. With the exception of chlorpheniramine and mepyramine, all tested antihistaminics produced hypothermia in mice, although fife of them (chlorpheniramine, diphenhydramine, chlorcyclizine, chloropyramine and thenalidine) antagonized the reserpine-induced hypothermia. With the exception of mepyramine and clemastine, the compounds tested shortened the period of immobility of rats in the behavioral despair test. The results indicate that only few antihistaminics have pharmacological profile resembling tricyclic or atypical antidepressant drugs.