1.Pharmacological characterization and appetite suppressive properties of BMS-193885, a novel and selective neuropeptide Y(1) receptor antagonist.
Antal-Zimanyi I1, Bruce MA, Leboulluec KL, Iben LG, Mattson GK, McGovern RT, Hogan JB, Leahy CL, Flowers SC, Stanley JA, Ortiz AA, Poindexter GS. Eur J Pharmacol. 2008 Aug 20;590(1-3):224-32. doi: 10.1016/j.ejphar.2008.06.032. Epub 2008 Jun 12.
Treatment of obesity is still a large unmet medical need. Neuropeptide Y is the most potent orexigenic peptide in the animal kingdom. Its five cloned G-protein couple receptors are all implicated in the regulation of energy homeostasis evidenced by overexpression or deletion of neuropeptide Y or its receptors. Neuropeptide Y most likely exerts its orexigenic activity via the neuropeptide Y(1) and neuropeptide Y(5) receptors, although the involvement of the neuropeptide Y(2) and neuropeptide Y(4) receptors are also gaining importance. The lack of potent, selective, and brain penetrable pharmacologic agents at these receptors made our understanding of the modulation of food intake by neuropeptide Y-ergic agents elusive. BMS-193885 (1,4-dihydro-[3-[[[[3-[4-(3-methoxyphenyl)-1-piperidinyl]propyl]amino] carbonyl]amino]phenyl]-2,6-dimethyl-3,5-pyridinedicarboxylic acid, dimethyl ester) is a potent and selective neuropeptide Y(1) receptor antagonist.