Prospects for obesity treatment: MCH receptor antagonists

The convergence of the orphan G protein-coupled receptor SLC-1 with its orexigenic neuropeptide ligand melanin-concentrating hormone (MCH) in 1999 stimulated considerable research activity aimed at characterizing the role of this receptor system in the regulation of body weight. A solid body of genetic and pharmacological evidence now supports a role for MCH in the modulation of food intake and energy expenditure. High-throughput screening efforts have led to the identification of small molecule MCH receptor antagonists with diverse structural features and drug-like properties. In vivo results with two of these antagonists indicate efficacy in several animal models of body weight regulation and feeding behavior. Based on these preclinical findings, it is likely that reports from clinical studies of MCH antagonists will soon be forthcoming.