In this chapter we review the development of melanin concentrating hormone receptor 1
(MCH-R1) antagonists as a new perspective for the pharmacological treatment of obesity. We will
initially focus on melanin concentrating hormone (MCH): structure, localization and function in the
regulation of feeding behavior and energy balance and two receptors for MCH in humans. We will
then review the discovery of the first MCH-R1 antagonists, the drug-design strategies used to
obtained new series of MCH-R1 antagonists and an analysis of their structure-activity relationship.
Finally, we will evaluate the absorption, distribution, metabolism and excretion, efficacy, safety and
toxicity in preclinical and clinical trials.
Keywords: Development, Melanin concentrating hormone (MCH), Melanin concentrating hormone
receptor 1 (MCH-R1), Structure-activity relationship (SAR), Obesity.
