Serotonin reuptake inhibitors fluoxetine and citalopram relax intestinal smooth muscle

P. Pacher, Z. Ungvari, V. Kecskeméti, T. Friedmann, S. Furst

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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 × 10-7 M, 1.4 × 10-6 M, 1.4 × 10-5, and 6.8 × 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 × 10-8 M, 1.4 × 10-7 M, 3.7 × 10-6 M, and 6.3 × 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.

Original languageEnglish
Pages (from-to)580-584
Number of pages5
JournalCanadian journal of physiology and pharmacology
Issue number7
Publication statusPublished - Jan 1 2001



  • Citalopram (Seropram®)
  • Diltiazem
  • Fluoxetine (Prozac®)
  • Intestinal smooth muscle
  • L-type Ca channels
  • Nifedipine

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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