Modulation of neuropeptide Y receptors for the treatment of obesity

Abstract

Background: Neuropeptide Y (NPY) has been demonstrated to have critical roles in the physiological control of appetite and energy homeostasis through NPY Y1, Y2, Y4 and Y5 receptors. A number of synthetic ligands for NPY receptor subtypes have been developed to date, with Y5 receptor antagonists and Y2 and Y4 receptor agonists advancing into clinical trials. Methods: A survey of the scientific and patent literature since mid-2006 is presented. Conclusion: In addition to the specific modulation of respective NPY receptor subtypes, recent investigations have revealed that modulation of multiple NPY receptor subtypes produces additive or even synergistic anti-obesity effects. Development of reliable small molecule Y1, Y2 and Y4 receptor ligands would greatly accelerate investigations and drug discovery.

Keywords::

• anti-obesity
• neuropeptide Y
• NPY receptor antagonist/agonist
• receptor subtypes

Acknowledgement

The authors thank PT Meinke (Merck Research Laboratories, Rahway, NJ) for the editing of this manuscript.