Dose-response relationships in the thermoregulatory effects of capsaicin.

The hypothermic effect of capsaicin, the reduced responsiveness towards the hypothermic effect of the drug as well as the impairment of thermoregulation in the warm environment subsequent to the administration of different doses of capsaicin have been studies in rats. The mortality after capsaicin treatment has also been established. 1. Capsaicin given subcutaneously in doses of 1-10 mg/kg induced a dose-dependent fall in body temperature lasting for 2-5 h. A single dose of 10 mg/kg caused the most pronounced hypothermic effect reaching its maximum (3,4 degrees C) after 107 min. After higher doses (20-50 mg/kg) the fall in body temperature was less, being similar to that observed after the administration of 1-2 mg/kg. 2. A decreased sensitivity towards the hypothermic effect of a test dose of 2 mg/kg capsaicin, as well as an impaired tolerance to high ambient temperature have been found in rats 2 weeks after the pretreatment either with a single dose of 20-50 mg/kg or fractionated administration of 50 mg/kg capsaicin. The fractionated administration of a dose of 50 mg/kg capsaicin proved to be beneficial in decreasing mortality without affecting the desensitizing effect of capsaicin pretreatment. 3. After single doses of capsaicin the hypothermic period was followed by a dose-dependent hyperthermia which lasted for at least 2 days. A close correlation between the prolonged hyperthermic action and the desensitizing effect of capsaicin administration has also been established. The possible relationship between the desensitizing and hyperthermia inducing effect of capsaicin is briefly discussed.