Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults.
Cell Metab
; 4(4): 275-82, 2006 Oct.
Article
en En
| MEDLINE
| ID: mdl-17011500
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Compuestos de Espiro
/
Receptores de Neuropéptido Y
/
Fármacos Antiobesidad
/
Ciclohexanos
/
Obesidad
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
Límite:
Adolescent
/
Adult
/
Aged
/
Humans
/
Middle aged
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2006
Tipo del documento:
Article