Mianserin hydrochloride: Peripheral and central effects in relation to antagonism against 5-hydroxytryptamine and tryptamine

Abstract

Mianserin hydrochloride, a new anti-5-hydroxytryptamine agent, was compared with cyproheptadine with respect to a variety of responses evoked by 5-hydroxytryptamine and other agonists. Central effects against tryptamine responses and general depressant effect on CNS were also studied. The two antagonists induced comparable inhibition against responses in which D-receptors of 5-HT were involved. Mianserin displayed α-adrenolytic activity and did not antagonize muscarinic effects of acetylcholine; the opposite was true for cyproheptadine. Mianserin was more effective than cyproheptadine in counteracting tryptamine-induced responses in rabbits and rats. Cyproheptadine produced diffuse depression of the CNS, with marked elevation of the threshold to electric stimulation of the brain stem reticular system in rabbits, persistent block of the acoustic arousal in rats and rabbits and prolongation of barbiturate sleep in rats. Mianserin however did not produce CNS depression, other than transient inhibition of the sensory activation of the EEG in rabbits. The earlier postulated structure-activity relationship between mianserin and cyproheptadine does not appear to apply to effects other than certain 5-HT responses and central tryptamine effects.