INFLUENCE OF GRANISETRON ON THERMOREGULATION DURING EXERCISE IN THE HEAT

Background: A NATO project group has an interest in selecting an antie metic agent that not only is effective in the prevention of emesis ind uced by chemical agents or radiation exposure but also has minimal, if any, side effects. Granisetron is the second candidate drug of a clas s of selective serotonin antagonists that has been shown to be an effe ctive antiemetic agent for patients receiving radiation or chemotherap y treatment. The present study was designed to evaluate whether a sing le 2-mg oral dose of granisetron influenced temperature regulation dur ing exercise in a hot and relatively dry environment. Hypothesis: Base d on our previous findings with the other candidate drug, ondanseton, we hypothesized that granisetron would not influence temperature regul ation. Methods: Nine unacclimatized males performed a drug and placebo trial in a double-blind manner. The sessions involved walking on a tr eadmill 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. Results: Granisetron was associated with a small (0.2 degrees C) but s ignificant elevation in mean skin temperature at the beginning and aft er 2 h of exercise. However, there was no difference between trials fo r the 1.6 degrees C increase in rectal temperature. Also, body heat ga in (406 +/- 97 and 407 +/- 103 kj for the placebo and drug trial, resp ectively) 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 n ot different. Tolerance times also were not different for the placebo (157.4 +/- 16.7 min) and drug (159.4 +/- 20.4 min) sessions. Conclusio ns For the environmental conditions used in this investigation, we wou ld accept the null hypothesis that a single 2 mg oral dose of graniset ron does not influence temperature regulation during exercise.