Melanocortin

Appetite-suppressing. Neuropqrtide modulators and gut hormones with anorexigenic effects are a-melanocortin-stimulating hormone (a-MSH), cocaine- and amphetamine-regulated transcript (CART), glucagon-like peptide-1 (GLP-1), leptin, insulin, oxyntomodulin, pancreatic peptide PP, peptide YY and PYY3 36, and others. 

Formerly known as PT-141 from Palatin Technologies is in phase 2 clinical trials. It is a melanocortin receptor agonist and is being trialled for male and female sexual dysfunction and is believed to have none of the cardiovascular effects possibly associated with other therapies. 

Melanocortin peptides have been proposed as potent modulators of many pathologies including inflammatory (asthma, arthritis) and cardiovascular disease. They have been shown to be directed against resident cells within tissue such as macrophages, endothelial cells and also circulating leukocytes (neutrophils and lymphocytes). Therefore harnessing their therapeutic potential could lead to the development of novel therapeutics. 

Melanocortins were identified in common ancestors of lampreys and gnathostomes over 700 million years ago and are little changed throughout evolution. They... 

MC3R is expressed both within the periphery and central nervous system (CNS) with detection in immune cells, gut, placenta but no detection in the adrenal gland or melanocytes. Unlike other MCR, most melanocortins (ACTHi 39, a-, (3- and y-MSH) display equipotent binding and full biological activity with truncated peptides, ACTH o and ACTH o MC3R... 

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

Melanocortins. Figure 1 Shows the melanocortin receptors, function and naturally occurring peptide sequences that activate them. 

Cardiovascular disease affects 2.7 million British people and is a major cause of mortality with circulating neutrophils being proposed as contributing factors in ischaemic damage, though damage can still occur in vitro in the absence of blood. Melanocortins have... 

Melanocortins. Figure 2 Shows anti-inflammatory effect of melanocortin peptides. 

Melanocortins. Figure 3 Melanocortins have the potential to restore homeostasis to tissue. 

MC4R for feeding behaviour, targeting one or both of these recqDtors in addition to understanding the complex cross-talk within the CNS may lead to the development of melanocortin based therapeutics for the treatment of eating disorders [5]. 

Melanocortin peptides are potent anti-inflammatory agents displaying beneficial effects in diseases ranging from cardiovascular to arthritis to obesity to name a few. Within an inflammatory context, they have the ability to switch off early production of cytokines and at later stages they increase levels of anti-inflammatory proteins that lead to the resolution of the host inflammatory response potentially restoring homeostasis to the tissue. They could eventually be viewed as an alternative to glucocorticoids, as their mode of action often resembles that seen... 

Getting SJ (2006) Targeting melanocortin receptors as potential novel therapeutics. Pharmacol Ther 111 1-15... 

Wikberg JE, Muceniece R, Mandrika I, Pmsis P, LindblomJ, Post C, Skottner A (2000) New aspects on the melanocortins and their receptors. Pharmacol Res 42 393 120... 

Catania A, Gatti S, Colombo G et al (2004) Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 56 1—29... 

Cone RD (2006) Studies on the physiological functions of the melanocortin system. EndocrRev 27 736-749... 

MDR-ABC Transporters Mechanism-based Inhibition Meglitinide-related Compounds Melanin-concentrating Hormone Melanocortins... 

Other peptides that have been linked to the actions of ethanol are corticotropin-releasing factor, urocortin, leptin, cholecystokinin, melanocortins, and galanin (for reviews, see Cowen et al. 2004 Egli 2003 Thiele et al. 2003). 

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