Melanin-Concentrating Hormone MCH1 Receptor Antagonists

Toshiharu Shimazaki, Takao Yoshimizu, Shigeyuki Chaki

Melanin-concentrating hormone (MCH) is a cyclic 19-amino-acid neuropeptide that has been considered to play a key role in the regulation of feeding and energy homeostasis. To date, two receptor subtypes for MCH (designated MCH(1) and MCH(2)) have been identified; the MCH(1) receptor has been proposed to mediate the physiological functions of MCH in rodents. In addition to the crucial roles of MCH in feeding behaviour, anatomical and neurochemical studies suggest that the MCH/MCH(1) system is involved in the regulation of emotion and stress responses. This assumption has been supported by a recent series of neurochemical and behavioural studies. Indeed, several lines of evidence show that MCH activates stress responses and induces depressive- and anxiety-like behaviours, while the blockade of MCH(1) receptors results in antidepressant and anxiolytic effects in various rodent models. Moreover, MCH may decrease reward activity while increasing hypothalamus-pituitary adrenal axis activity, both of which may underlie the neurochemical mechanisms of the depression and anxiety-like effects induced by MCH. The effects of MCH(1) receptor antagonists in animal models, together with their rapid onset of effect and lack of adverse CNS effects, suggest that they deserve further investigation as potential new treatments for depression and anxiety disorders.