Abstract：
:Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonism of NPY Y1 and NPY Y5 receptors (NPYxR) is considered a potentially important anti-obesity drug target. We tested the hypothesis that blockade of the NPY5R will lead to weight loss in humans using MK-0557, a potent, highly selective, orally active NPY5R antagonist. The initial series of experiments reported herein, including a multiple-dose positron-emission tomography study and a 12 week proof-of concept/dose-ranging study, suggested an optimal MK-0557 dose of 1 mg/day. The hypothesis was then tested in a 52 week, multicenter, randomized, double-blind, placebo-controlled trial involving 1661 overweight and obese patients. Although statistically significant at 52 weeks, the magnitude of induced weight loss was not clinically meaningful. These observations provide the first clinical insight into the human NPY-energy homeostatic pathway and suggest that solely targeting the NPY5R in future drug development programs is unlikely to produce therapeutic efficacy.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Erondu N,Gantz I,Musser B,Suryawanshi S,Mallick M,Addy C,Cote J,Bray G,Fujioka K,Bays H,Hollander P,Sanabria-Bohórquez SM,Eng W,Långström B,Hargreaves RJ,Burns HD,Kanatani A,Fukami T,MacNeil DJ,Gottesdiener KM,Amadoi
10.1016/j.cmet.2006.08.002subject
Has Abstractpub_date
2006-10-01 00:00:00pages
275-82issue
4eissn
1550-4131issn
1932-7420pii
S1550-4131(06)00272-5journal_volume
4pub_type
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