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Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats

Eur J Pharmacol. 2006 Feb 27;532(3):258-64. doi: 10.1016/j.ejphar.2005.12.075. Epub 2006 Feb 20.

Abstract

5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / enzymology
  • Clorgyline / toxicity
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Fluvoxamine / toxicity
  • Male
  • Monoamine Oxidase Inhibitors / toxicity*
  • Motor Activity / drug effects
  • Pargyline / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / toxicity*
  • Selegiline / toxicity
  • Serotonin
  • Serotonin Syndrome / etiology*
  • Serotonin Syndrome / metabolism

Substances

  • Monoamine Oxidase Inhibitors
  • Serotonin Uptake Inhibitors
  • Selegiline
  • Serotonin
  • Pargyline
  • Clorgyline
  • Fluvoxamine