EFFECT OF ETOPERIDONE, A NEW POTENTIAL ANTI-DEPRESSANT DRUG, ON THE CENTRAL SEROTONIN SYSTEM

The effect of etoperidone-a non-tricyclic potential antidepressant drug-on the central serotonergic system was studied. It was demonstrated that this compound inhibited the head twitch reaction induced by 5-HTP in mice and rats (ED50 values amounted to 2.89 and 2.29 mg/kg i.p. respectively). In the flexor reflex preparation in spinal rats etoperidone used in doses lower than 1 mg/kg i.v. produced no effect, while doses of 1 mg/kg i.v. and higher had a stimulating action which occured 10-15 min after injection. This stimulating action was abolished by 5-HT antagonists (cyproheptadine, danitracen) and by the drug metabolism inhibitor SKF-525 A, but not by the 5-HT uptake inhibitor clomipramine. Etoperidone given in a dose of 0.5 mg/kg i.v. had no effect on the stimulating action of serotoninmimetics (LSD, quipazine, fenfluramine) on the flexor reflex, but it abolished the effect of LSD in rats pretreated with SKF-525A. The above findings indicate that etoperidone has a biphasic action on the serotonergic transmission, revealing characteristics of the 5-HT antagonist and agonist. The agonistic action is probably connected with the formation of a metabolite. © 1979 Springer-Verlag.