Tiflucarbine is a thieno[3,2-e]indole derivative patented by Troponwerke G.m.b.H. und Co. K.-G. as antidepressant. Tiflucarbine acts as a potent inhibitor of the 5-hydroxytryptamine (5-HT) uptake and has no effect on 5-HT2 postsynaptic receptors. In preclinical models, Tiflucarbine down-regulates the noradrenaline responses of the cAMP system in rats cerebral cortex. Tiflucarbine treatment increased the specific activity of soluble calmodulin (CaM)-dependent phosphodiesterase in rat brain. Tiflucarbine bound to CaM and inhibited its interaction with the phosphodiesterase. Adrenergic denervation by 6-hydroxydopamine injection prevented both the beta-adrenoceptor down-regulation and the increase in the specific activity of the phosphodiesterase. Tiflucarbine exerted no effect on the reserpine hypothermia, attenuated the apomorphine hypothermia and enhanced the TRH-induced hyperthermia. It did not prevent tryptamine convulsions or the fenfluramine-induced hyperthermia and inhibited the L-5-hydroxytryptophan-induced head twitches. Tiflucarbine administered repeatedly enhanced the D-amphetamine-induced locomotor hyperactivity and inhibited the clonidine-induced aggressiveness.