title: Studies on the effects of antidepressant drugs on the antinociceptive action of morphine and on plasma morphine in rat and man.
abstract: In the rat we studied the effect of 3 tricyclic antidepressants: chlorimipramine, amitriptyline and nortriptyline, and the atypical antidepressant trazodone on pain thresholds when administered alone or together with morphine. Moreover, we evaluated the effect of the antidepressants on free morphine plasma concentrations both in the rat and in man. We observed that chlorimipramine and amitriptyline, two tricyclic antidepressants active on the serotoninergic system, induce analgesia and potentiate morphine analgesia in a dose-related fashion. The noradrenergic tricyclic nortriptyline and trazodone did not elicit analgesia and inconsistently affected morphine analgesia. In the rat, all drugs tested increased plasma concentrations of morphine with the exception of amitriptyline. In man, only chlorimipramine and amitriptyline increased the plasma concentration of the free opiate.
authors.affiliation: Department of Pharmacology, University of Milan, 20129 Milan Italy Pain Therapy Division, National Cancer Institute, 20133 Milan Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Ventafridda
authors.forename: Mauro
authors.initials: M
authors.lastname: Blanchi
authors.forename: Caria
authors.initials: C
authors.lastname: Ripamonti
authors.forename: Paola
authors.initials: P
authors.lastname: Sacerdote
authors.forename: Franco
authors.initials: F
authors.lastname: De Conno
authors.forename: Ernesto
authors.initials: E
authors.lastname: Zecca
authors.forename: Alberto E
authors.initials: AE
authors.lastname: Panerai
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D009020:Morphine / Q000097:blood*; D009661:Nortriptyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014196:Trazodone / Q000494:pharmacology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D009020:Morphine; D009661:Nortriptyline; D002997:Clomipramine; D014196:Trazodone