Inhibition of gastric emptying and feeding by fenfluramine

To assess the mechanism by which the anorectic agent fenfluramine influences feeding, we examined in Macaca mulatta the effect of intragastric fenfluramine (2 mg/kg) on both feeding and the gastric emptying of saline and glucose test meals. Gastric emptying was measured by the dye-dilution technique, using chronic indwelling intragastric cannulas. The emptying of normal saline was inhibited by fenfluramine as was the initial bolus phase of the emptying of glucose. In contrast, the subsequent controlled phase of glucose emptying was unaffected in two out of four animals, slightly inhibited in one, and strongly inhibited in only one monkey. Rhesus monkeys trained to drink a glucose solution to satiety drank, on average, 21% less after fenfluramine. The emptying of the consumed glucose solution from the stomach was reduced by 39%, whereas gastric volume at satiety was reduced by only 10%. The reduction of intake was strongly related to the degree of inhibition of gastric emptying. These results support an important role for the inhibition of gastric emptying in fenfluramine-induced suppression of feeding.