Detrimental effects of tropisetron on permanent ischemic stroke in the rat

BMC Neurosci. 2008 Feb 6;9:19. doi: 10.1186/1471-2202-9-19.

Abstract

Background: Recent in vitro evidence indicates that blockade of 5-hydroxytryptamine (5-HT) receptor 3 (5-HT3) is able to confer protection in different models of neuronal injury. The purpose of the present study was to investigate the effect of tropisetron, a 5-HT3 receptor antagonist, on infarct size and neurological score in a model of ischemic stroke induced by permanent middle cerebral artery occlusion (pMCAO) in the rat.

Methods: Two different doses of tropisetron (5 and 10 mg/kg) or vehicle were administered intraperitoneally 30 min before pMCAO. Neurological deficit scores, mortality rate and infarct volume were determined 24 h after permanent focal cerebral ischemia.

Results: Tropisetron failed to reduce cerebral infarction. Animals receiving tropisetron showed a significant increase (p < 0.05) in neurological deficits and mortality rate.

Conclusion: Data from this study indicate that blockade of 5-HT3 receptors with tropisetron worsens ischemic brain injury induced by pMCAO. These findings could have important clinical implications. Patients taking tropisetron, and possibly other 5-HT3 antagonists, could potentially have a worse outcome following a brain infarct.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Infarction / drug therapy*
  • Brain Infarction / etiology*
  • Brain Infarction / mortality
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Indoles / therapeutic use*
  • Infarction, Middle Cerebral Artery / complications*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / mortality
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Antagonists / therapeutic use*
  • Severity of Illness Index
  • Tetrazolium Salts
  • Tropisetron

Substances

  • Indoles
  • Serotonin Antagonists
  • Tetrazolium Salts
  • Tropisetron
  • triphenyltetrazolium