Doxepin as a blocker of central serotonin receptors.

The antidepressant drug-Doxepin (DX) was examined in order to investigate its central antiserotonin activity. The drug antagonized the behavioral syndrome elecited by L-5-hydroxytryptophan in rats and mice, but did not affect the pinna reflex. In the flexor reflex preparation, DX acted like other sero-tonin receptor blockers: By itself, it had no influence on the flexor reflex but it prevented the potentiation induced by serotonergic agents (fenfluramine, LDS, mescaline). The hyperthermia provoked by serotonergic agent (fenfluramine, LSD)in rabbits was antagonized by DX. DX abolished the syndrome induced by oxotremorine. The results obtained indicate that DX blocks central 5-HT receptors, like the two other antidepressants, mianserin and danitracen.