Neuropeptide Y receptors as targets for anti-obesity drug development: perspective and current status.

Abstract

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.

• Authors: Eric Parker, Margaret Van Heek, Andrew Stamford
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 440 Issue 2-3 Pg. 173-87 (Apr 12 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12007534 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Obesity Agents
• BIBP 3226
• Neuropeptide Y
• Pharmaceutical Preparations
• Receptors, Neuropeptide Y
• Arginine

Topics

• Animals
• Anti-Obesity Agents (chemistry, pharmacology)
• Arginine (analogs & derivatives, chemistry, pharmacology)
• Body Weight (drug effects, physiology)
• Energy Metabolism (drug effects, physiology)
• Humans
• Neuropeptide Y (physiology)
• Obesity (drug therapy, physiopathology)
• Pharmaceutical Preparations (chemistry)
• Receptors, Neuropeptide Y (antagonists & inhibitors, physiology)
• Structure-Activity Relationship