The effect of etoperidone, a new potential antidepressant 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 occurred 10--15 min after injection. This stimulating action was abolished by 5-HT antagonists (cyproheptadine, danitracen) and by the drug metabolism inhibitor SKF-525A, 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.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D014196:Trazodone / Q000031:analogs & derivatives / Q000494:pharmacology*
D000928:Antidepressive Agents; D010879:Piperazines; D012701:Serotonin; C013528:etoperidone; D014196:Trazodone