title: Comparison of the anticholinergic effects of the serotonergic antidepressants, paroxetine, fluvoxamine and clomipramine.
abstract: Paroxetine, a selective serotonin reuptake inhibitor, shows relatively high affinity for muscarinic acetylcholine receptors compared to other selective serotonin reuptake inhibitors. To determine whether paroxetine has anticholinergic effects in vivo, we examined the effects of paroxetine on oxotremorine-induced tremor, spontaneous defecation and passive avoidance performance using mice and compared the results with those using fluvoxamine, another selective serotonin reuptake inhibitor, and clomipramine, a tricyclic antidepressant with serotonin selectivity. The potency of antidepressant activity as determined in the tail suspension test was paroxetine>fluvoxamine>clomipramine. Paroxetine and clomipramine inhibited oxotremorine-induced tremor, reduced spontaneous defecation and impaired passive avoidance performance, while fluvoxamine did not have similar effects. A comparison of ED(50) values showed that the ratio of anticholinergic effect to antidepressant activity was fluvoxamine, >3.2; paroxetine, 2.1-2.6; clomipramine, <0.8. These results suggest that paroxetine may induce fewer adverse anticholinergic effects than clomipramine, but more than fluvoxamine.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku, Yokohama 222-8567, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Fujishiro
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Imanishi
authors.forename: Kaname
authors.initials: K
authors.lastname: Onozawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Tsushima
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D003672:Defecation / Q000187:drug effects / Q000502:physiology; D016666:Fluvoxamine / Q000494:pharmacology*; D007103:Immobilization / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D017374:Paroxetine / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D018680:Cholinergic Antagonists; D002997:Clomipramine; D016666:Fluvoxamine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors