Detrimental effects of tropisetron on permanent ischemic stroke in the rat.
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.


CONCLUSIONS
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.
Candelario-Jalil
Eduardo
E
Neurochemistry Research Group, Department of Psychiatry, University of Freiburg Medical School, Hauptstr, 5, D-79104 Freiburg, Germany. ecandelario-jalil@salud.unm.edu
Muñoz
Eduardo
E
Fiebich
Bernd L
BL
D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013778:Tetrazolium Salts; D000077526:Tropisetron
D007211:Indoles; D012702:Serotonin Antagonists; D013778:Tetrazolium Salts; D000077526:Tropisetron; C009591:triphenyltetrazolium