In mammals, Melanin Concentrating Hormone (MCH), a GPCR, has been shown to regulate food consumption and energy metabolism. Central administration of MCH has been shown to promote feeding while mRNA levels of the MCH Receptor 1 (MCHR1) rise as a result of starvation and leptin deficiency. MCH also stimulates insulin and leptin relase in insulinoma cell lines and adipose cells respectively and regulates pituitary hormones. Mice devoid of MCH are lean and hypophagic, while mice over-expressing MCH are obese and hyperphagic. Genetic disruption of MCHR1 on the other hand results in mice that are hyperphagic, but also hypermetabolic and obesity-resistant.
University of California, Irvine researchers have found a class of small molecule MCHR1 antagonists that specifically inhibits MCH activation of MCHR1. These compounds display no affinity to human MCH2R and other peptide GPCRs. To demonstrate the efficacy in vivo, these compounds were administered in rats and MCH-induced food intake was reduced up to 75% in a dose dependent manner. The effects of these compounds lasted for over four hours. These compounds do not affect locomotion or fine movements, and also do not result in ataxis movements
These compounds are efficacious in reducing food intake in rats and may be useful for the treatment of conditions associated with the MCH receptor in humans such as obesity, diabetes, eating disorders and related conditions.
|United States Of America||Issued Patent||8,372,848||02/12/2013||2003-546|