The MC4 receptor as a drug discovery target

Abstract

Molecular and pharmacological studies have provided valuable information for elucidating the biological functions of the central melanocortin system, which includes the MC 3 and MC 4 receptor subtypes and their endogenous ligands. Compelling evidence demonstrates that the MC 4 receptor plays an important role in feeding behavior, energy homeostasis, sexual function, nociception, drug addiction and stress responses. Potent and selective MC 4 receptor ligands are vital to define the physiological roles of this receptor. Preclinical studies have proven that selective MC 4 receptor agonists reduce food intake and body weight and increase erectile activity. Selective MC 4 receptor antagonists alleviate cachectic syndrome, neuropathic pain, the motivational effects of addictive drugs and stress-induced depression and anxiety. Clinical studies have shown that the neural MC 3 /MC 4 receptor dual agonist MTII elicits erectile responses in healthy volunteers and in patients with erectile dysfunction. In this review, we summarize the recent development of small-molecule MC 4 receptor ligands and evidence concerning the involvement of this receptor in various physiological functions. Within this context, we attempt to provide an insight into the potential therapeutic uses of MC 4 receptor ligands.