Granisetron shows no pro-arrhythmic effect in normal subjects during or after exercise in a hot environment.
BACKGROUND
5-HT3 receptor antagonists are being evaluated as possible agents to prevent nausea and vomiting associated with radiation exposure in a non-clinical military setting. Because of concern about potential cardiovascular toxicity and the observation that certain developmental 5-HT3 antagonists produced undesirable effects, all drugs in this class are being carefully scrutinized for possible adverse cardiac effects.


METHODS
In this study, nine subjects underwent ambulatory ECG monitoring for an average of 21.6 h after a 2-mg oral dose of granisetron or placebo in a double-blind crossover protocol. Monitoring included a 3-h period of submaximal exercise in a 40 degrees C environment.


RESULTS
Although isolated ventricular and supraventricular ectopic activity, sinus bradycardia, and pauses were found, there were no sustained arrhythmias observed in either the placebo or granisetron conditions.


CONCLUSIONS
Although the generalizability of this study is limited by the small number of subjects, these observations add to the body of evidence confirming the lack of cardiovascular toxicity of granisetron.
Gray
G W
GW
Defence and Civil Institute of Environmental Medicine, Downsview, Ont., Canada.
McLellan
T M
TM
Ducharme
M B
MB
D000284:Administration, Oral; D001833:Body Temperature Regulation / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D015444:Exercise / Q000502:physiology*; D017829:Granisetron / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D008297:Male; D012016:Reference Values; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D017829:Granisetron; D012702:Serotonin Antagonists