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 pharmacokinetic (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.
|
Authors | Douglas J MacNeil |
Journal | Current topics in medicinal chemistry
(Curr Top Med Chem)
Vol. 7
Issue 17
Pg. 1721-33
( 2007)
ISSN: 1873-4294 [Electronic] United Arab Emirates |
PMID | 17979781
(Publication Type: Journal Article, Review)
|
Chemical References |
- Anti-Obesity Agents
- Receptors, Neuropeptide Y
- neuropeptide Y-Y1 receptor
- neuropeptide Y5 receptor
|
Topics |
- Animals
- Anti-Obesity Agents
(pharmacology)
- Humans
- Obesity
(drug therapy, metabolism)
- Receptors, Neuropeptide Y
(antagonists & inhibitors, metabolism, physiology)
|