The effect of methysergide and other receptor antagonists on fenfluramine-induced glucose uptake into the isolated rat hemidiaphragm.

Fenfluramine in therapeutic concentrations causes a significant and dose related increase in glucose uptake into isolated rat and human skeletal muscle in the presence of insulin. Using fenfluramine, 100 ng/ml, on the rat hemidiaphragm preparation the effects of the following receptor blocking drugs in concentrations up to 250 ng/ml were investigated on this phenomenon: atropine, haloperidol, mepyramine, methysergide, propranolol and thymoxamine. Only methysergide, the 5-HT antagonist, reduced the action of fenfluramine in relatively low concentrations of the drug which were dose related (10 ng/ml causing approximately 40% inhibition). This suggests that the peripheral as well as the central actions of fenfluramine are mediated through 5-HT receptors.