Food intake inhibition and reduction in body weight gain in rats treated with GI264879A, a non-selective NPY-Y1 receptor antagonist

Neuropeptide Y has been proposed to play a major role in the hypothalamic r egulation of feeding behavior through the activation of specific, central N PY receptor(s). In an effort to design small molecule antagonists of NPY re ceptors, we have synthesized a series of substituted dipeptides based on de fined pharmacophores, previously identified by us and others as essential f or the interaction with the peptide receptors. G1264879A behaves as a funct ional antagonist of Y1 receptors while displaying no binding selectivity fo r the different NPY receptor subtypes. We demonstrate here that administrat ion of G1264879A to rats causes a significant decrease in food intake and b ody weight partly through a mechanism dependent on the integrity of the vag us nerve. (C) 2001 Published by Elsevier Science Inc.