Some central effects of tiflucarbine, a new potential antidepressant drug.
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.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Rogóz
Z
Z
Sowińska
H
H
Zalewski
Z
Z
D000374:Aggression / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants; D000928:Antidepressive Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004347:Drug Interactions; D005277:Fenfluramine / Q000494:pharmacology; D006380:Helplessness, Learned; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D000927:Anticonvulsants; D000928:Antidepressive Agents; D007211:Indoles; D011942:Receptors, Adrenergic, alpha; D013876:Thiophenes; D005277:Fenfluramine; D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine; C050288:tiflucarbine; D003913:Dextroamphetamine