title: Serotonin reuptake inhibitors fluoxetine and citalopram relax intestinal smooth muscle.
abstract: Selective serotonin reuptake inhibitor antidepressants (SSRIs) exert depressant effects on cardiac myocytes and vascular smooth muscle cells by inhibiting Ca2+ channels. We hypothesized that the SSRIs fluoxetine and citalopram affect the contractile activity of intestinal smooth muscle by interfering with Ca2+ entry and (or) signaling pathways. The effects of fluoxetine and citalopram on contractions of guinea-pig ileum longitudinal muscle-myenteric plexus preparations (LMMP) were compared with the effects of the voltage-operated Ca2+ channel inhibitors nifedipine and diltiazem. In a concentration-dependent manner, nifedipine, diltiazem, fluoxetine, and citalopram elicited relaxation of LMMPs contracted by electrical field stimulation (EC50 values of 4 x 10(-7) M, 1.4 x 10(-6) M, 1.4 x 10(-5), and 6.8 x 10(-6) M, respectively). Nifedipine, diltiazem, fluoxetine, and citalopram also relaxed LMMPs contracted with a depolarizing concentration of KCl (48 mM; EC50 values of 1.8 x 10(-8) M, 1.4 x 10(-7) M, 3.7 x 10(-6) M, and 6.3 x 10(-6), respectively), a response that could be reversed by increasing the extracellular Ca2+ concentration (2.5-30 mM). These data suggest that fluoxetine and citalopram elicit relaxation of intestinal smooth muscle, likely by inhibiting Ca2+ channel(s). This effect may be of clinical importance.
authors.affiliation: Institute of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. ppacher@hotmail.com
authors.forename: P
authors.initials: P
authors.lastname: Pacher
authors.forename: Z
authors.initials: Z
authors.lastname: Ungvari
authors.forename: V
authors.initials: V
authors.lastname: Kecskeméti
authors.forename: T
authors.initials: T
authors.lastname: Friedmann
authors.forename: S
authors.initials: S
authors.lastname: Furst
mesh_terms: D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D015283:Citalopram; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors