Abstract
A combination of pharmacological and genetic studies in mice confirmed that the Y1 and Y5 receptors mediate the potent orexigenic actions of exogenous NPY. Although the physiological role of NPY in causing obesity is less clear, potent and selective antagonists of both Y1 and Y5 have been developed. Some of the NPY antagonists have suitable pharmokinetic (PK) properties that allowed them to be evaluated in various rodent models of obesity. Several different Y1 and Y5 antagonists cause weight loss in rodent models, though confirmation that these effects are mechanism based has been limited. One Y5 antagonist, MK-0557 was evaluated in a 1-yr clinical trial and found to cause modest weight loss. Optimal NPY antagonist therapeutics for obesity may require blockade of both the Y1 and Y5 receptors.
Keywords: Neuropeptide Y, Y1, Y5, receptor, antagonist, obesity
Current Topics in Medicinal Chemistry
Title: NPY Y1 and Y5 Receptor Selective Antagonists as Anti-Obesity Drugs
Volume: 7 Issue: 17
Author(s): Douglas J. MacNeil
Affiliation:
Keywords: Neuropeptide Y, Y1, Y5, receptor, antagonist, obesity
Abstract: A combination of pharmacological and genetic studies in mice confirmed that the Y1 and Y5 receptors mediate the potent orexigenic actions of exogenous NPY. Although the physiological role of NPY in causing obesity is less clear, potent and selective antagonists of both Y1 and Y5 have been developed. Some of the NPY antagonists have suitable pharmokinetic (PK) properties that allowed them to be evaluated in various rodent models of obesity. Several different Y1 and Y5 antagonists cause weight loss in rodent models, though confirmation that these effects are mechanism based has been limited. One Y5 antagonist, MK-0557 was evaluated in a 1-yr clinical trial and found to cause modest weight loss. Optimal NPY antagonist therapeutics for obesity may require blockade of both the Y1 and Y5 receptors.
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Cite this article as:
MacNeil J. Douglas, NPY Y1 and Y5 Receptor Selective Antagonists as Anti-Obesity Drugs, Current Topics in Medicinal Chemistry 2007; 7 (17) . https://dx.doi.org/10.2174/156802607782341028
DOI https://dx.doi.org/10.2174/156802607782341028 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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