Influence of granisetron on thermoregulation during exercise in the heat

A NATO project group has an interest in selecting an antiemetic agent that not only is effective in the prevention of emesis induced by chemical agents or radiation exposure but also has minimal, if any, side effects. Granisetron is the second candidate drug of a class of selective serotonin antagonists that has been shown to be an effective antiemetic agent for patients receiving radiation or chemotherapy treatment. The present study was designed to evaluate whether a single 2-mg oral dose of granisetron influenced temperature regulation during exercise in a hot and relatively dry environment.

Based on our previous findings with the other candidate drug, ondanseton, we hypothesized that granisetron would not influence temperature regulation.

Nine unacclimatized males performed a drug and placebo trial in a double-blind manner. The sessions involved walking on a treadmill at 4.8 km.h-1 with a 2% elevation for a maximum of 3 h at 40 degrees C and 30% relative humidity while wearing combat clothing.

Granisetron was associated with a small (0.2 degrees C) but significant elevation in mean skin temperature at the beginning and after 2 h of exercise. However, there was no difference between trials for the 1.6 degrees C increase in rectal temperature. Also, body heat gain (406 +/- 97 and 407 +/- 103 k) for the placebo and drug trial, respectively) and whole body sweat rates (0.72 +/- 0.10 and 0.73 +/- 0.10 kg.h-1 for the placebo and granisetron trial, respectively) were not different. Tolerance times also were not different for the placebo (157.4 +/- 16.7 min) and drug (159.4 +/- 20.4 min) sessions.

For the environmental conditions used in this investigation, we would accept the null hypothesis that a single 2 mg oral dose of granisetron does not influence temperature regulation during exercise.