Xylamidine

Xylamidine is a peripheral 5-HT receptor antagonist used to investigate possible peripheral appetite suppressant effects of 5-hydroxytryptophan (5-HTP) and fenfluramine. In a 1-hour food intake test, xylamidine attenuated the decrease in food intake induced by 5-HT and 5-HTP, but had no effect on fenfluramine, suggesting that the appetite suppressant effect of 5-HTP is mediated in part through peripheral 5-HT receptors. Microstructural analysis revealed that 5-HTP and fenfluramine induced a decrease in food intake rate and a reduction in feeding batch size. Xylamidine reversed the effects of 5-HTP on food intake rate and induced a slight increase in feeding batch size itself, thus, the peripheral effect of 5-HTP appears to be to slow food intake rate. No effect of xylamidine on fenfluramine-induced changes in feeding was observed. The results suggest that the appetite suppressant effects of 5-HTP and fenfluramine are differentiated based on the peripheral effects of 5-HTP. The peripheral effects of 5-HTP are distinct from the previously reported 5-HT-induced decreases in feeding batch size and duration. Possible mechanisms underlying the differences in peripheral effects of 5-HT and 5-HTP are discussed.

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