Neuropeptide Y receptors as targets for anti-obesity drug development: perspective and current status.
Neuropeptide Y is a widely distributed neuropeptide that elicits a plethora of physiological effects via interaction with six different receptors (Y(1)-y(6)). Recent attention has focused on the role of neuropeptide Y in the regulation of energy homeostasis. Neuropeptide Y stimulates food intake, inhibits energy expenditure, increases body weight and increases anabolic hormone levels by activating the neuropeptide Y Y(1) and Y(5) receptors in the hypothalamus. Based on these findings, several neuropeptide Y Y(1) and Y(5) receptor antagonists have been developed recently as potential anti-obesity agents. In addition, mice lacking neuropeptide Y, the neuropeptide Y Y(1) receptor or the neuropeptide Y Y(5) receptor have been generated. The data obtained to date with these newly developed tools suggests that neuropeptide Y receptor antagonists, particularly neuropeptide Y Y(1) receptor antagonists, may be useful anti-obesity agents. However, the redundancy of the neurochemical systems regulating energy homeostasis may limit the effect of ablating a single pathway. In addition, patients in whom the starvation response is activated, such as formerly obese patients who have lost weight or patients with complete or partial leptin deficiency, may be the best candidates for treatment with a neuropeptide Y receptor antagonist.
Parker
Eric
E
Department of CNS and Cardiovascular Research, Schering-Plough Research Institute, Mail Stop K-15-2-2760, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. eric.parker@spcorp.com
Van Heek
Margaret
M
Stamford
Andrew
A
D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009478:Neuropeptide Y / Q000502:physiology; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology; D004364:Pharmaceutical Preparations / Q000737:chemistry; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; C092926:BIBP 3226; D009478:Neuropeptide Y; D004364:Pharmaceutical Preparations; D017476:Receptors, Neuropeptide Y; D001120:Arginine