Dissociation of the anorectic actions of 5-HTP and fenfluramine

The possible peripheral anorectic actions of 5-hydroxytryptophan (5-HTP) and fenfluramine were examined in food-deprived rats. In a 1-h feeding test the peripherally acting 5-HT antagonist, xylamidine, attenuated the reductions in food intake induced by 5-HT and 5-HTP but not fenfluramine. Thus, the anorectic action of 5-HTP appears to be mediated in part by peripheral 5-HT receptors. Microstructural analyses showed that 5-HTP and fenfluramine induced decreases in eating rate and bout size. Xylamidine reversed the effect of 5-HTP on eating rate, and induced a slight increase in bout size in its own right. Therefore, the peripheral effect of 5-HTP appears to be a slowing of eating rate. No effects of xylamidine on fenfluramine induced changes in feeding were observed. The results indicate a dissociation of the anorectic effects of 5-HTP and fenfluramine based on a peripheral action of 5-HTP. The peripheral action of 5-HTP differs from the previously reported reductions in bout size and bout duration induced by 5-HT. Possible mechanisms for this difference in the peripheral actions of 5-HT and 5-HTP are discussed.