title: Trazodone, a central serotonin antagonist and agonist.
abstract: We examined the effect of trazodone (TR), a non-tricyclic antidepressant drug with an unknown mechanism of action, as well as its supposed metabolites beta-(3-oxo-s-triazolo-[4, 3 a]-pyridin-2-yl-propionic acid (OTPA) and 1-(m-chlorophenyl)-piperazine (CPP) on the serotonin (5-HT) -system in a model of the hind limb flexor reflex of the spinal rat. When given alone at low doses (1 mg/kg) TR does not change the flexor reflex but counteracts its serotonergic stimulation induced by LSD, quipazine or fenfluramine. At higher doses (6--8 mg/kg), after a period of latency, it enhances the reflex; this effect is antagonized by the 5-HT receptor blockers (cyproheptadine, WA-335 and metergoline) but not by imipramine. From the two TR metabolites studied only CPP exerts an effect in the flexor reflex model. It considerably enhances (0.05--1 mg/kg) the reflex, this effect being antagonized by cyproheptadine, WA-335 and metergoline, but not by imipramine. Our findings indicate that TR has a double effect on the central 5-HT system: at low doses it acts as a 5-HT antagonist, whereas at higher ones--as a 5-HT agonist. The latter effect may be connected with formation of a metabolite, CPP, or a compound chemically related to CPP.
mesh_terms: D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D014196:Trazodone / Q000031:analogs & derivatives / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D010879:Piperazines; D012702:Serotonin Antagonists; D014230:Triazoles; D005277:Fenfluramine; D003533:Cyproheptadine; D012701:Serotonin; D011814:Quipazine; D008238:Lysergic Acid Diethylamide; D007099:Imipramine; D014196:Trazodone