Melanotropins as Drugs for the Treatment of Obesity and Other Feeding Disorders: Potential and Problems

Abstract

Current biological and pharmacological evidence suggests that the melanocortin 4 and melanocortin 3 receptors which are seven transmembrane G-protein coupled receptors (GPCRs) are involved in various aspects of energy balance and feeding behaviors in animals including humans. The natural endogenous ligands for these receptors are products of the gene pro-opiomelanocortin (POMC), and include α-melanocyte stimulating hormone, γ-melanocyte stimulating hormone and perhaps other modified products of POMC. Thus well designed agonists and antagonists of these ligands might serve as drugs for the treatment of feeding disorders. However, these melanotropin peptides also can have other biological activities that involve the MC3R and MC4R, and these other biological properties will need to be modulated in ligands that are likely to be useful drugs for feeding disorders. Current progress in these areas with special emphasis on the MC3R will be discussed along with possible new directions that might be fruitful in these important aspects of contemporary biology and medicine.

Apigenin isolated from the seeds of Perilla frutescens britton var crispa (Benth.) inhibits food intake in C57BL/6J mice

“…Neurons located in the ventromedial part of the ARC produce neuropeptide Y (NPY) and agouti-related protein (AgRP), which increase appetite (Gropp et al, 2005;Luquet et al, 2005), while neurons located primarily in the ventrolateral part of the ARC co-express "pro-opiomelanocortin" (POMC) and "cocaine and amphetamine-related transcript" (CART), both of which inhibit feeding (Germano et al, 2007;Millington, 2007;Valassi et al, 2008). Melanocortins are produced by the cleavage of pro-POMC and exert their effects by binding to G-protein-coupled melanocortin receptors (MCRs) (Cai et al, 2009). Five MCRs are known, but only the MC3 (MC3R) and MC4 (MC4R) receptors are expressed in the brain (Fan et al, 1997;Catania, 2008;Fu and van den Pol, 2008).…”

Retinal Conformation Governs pKaof Protonated Schiff Base in Rhodopsin Activation

“…Changes in both structure and dynamics underlie the reaction coordinates for GPCRs such as rhodopsin 18,19 , the β -adrenergic receptors 83–86 , and other GPCRs of remarkable significance to human biology 15,87,88 . For rhodopsin, the role of dynamics in its activation mechanism has been explored both through experimental 28,29,33,34 and theoretical 47,50 approaches.…”

Monogene und syndromale Krankheitsbilder bei morbider Adipositas

“…B. eine Blutdruckerhöhung bzw. eine ungewollte sexuelle Stimulation, zu verursachen [5]. Kürzlich wurde erstmals über eine erfolgreiche Studie zur Entwicklung eines solchen Peptids berichtet, sodass es für die Patienten mit diesen sehr seltenen, aber schwerwiegenden monogenen Adipositasformen in absehbarer Zeit gegebenenfalls eine kausale pharmakologische Therapieoption geben könn-te.…”