Some central effects of tiflucarbine, a new potential antidepressant drug

Abstract

Tiflucarbine (TVX P 4495), a new putative antidepressant drug (AD) with a chemical novel among AD's [9-ethyl-4-fluoro-1-methyl-7,8,9,10-tetrahydrothieno (3,2-e)-pyrido(4,3-b)indole lactate], a potent inhibitor of the 5-hydroxytryptamine (5-HT) uptake, was studied in rats and mice, mostly with regard to its possible effect on the noradrenaline (NA) uptake and 5-HT postsynaptic receptors. 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 (at a high dose only). It stimulated the hind limb flexor reflex preparation of the spinal rat in cyproheptadine-reversible manner. In the behavioral despair test it shortened the immobility time. Tiflucarbine administered repeatedly enhanced the D-amphetamine-induced locomotor hyperactivity and inhibited the clonidine-induced aggressiveness. The results indicate that tiflucarbine exhibits characteristics of a poor inhibitor of the NA uptake (irrespective of its strong inhibitory effect on the 5-HT uptake), and has no effect on 5-HT2 postsynaptic receptors. When used repeatedly, it enhances--like other AD--responsiveness of the central dopamine system.