Melanocortins in the Treatment of Male and Female Sexual Dysfunction

Abstract

Melanocortinergic agents are currently being investigated for a possible therapeutic role in male and female sexual dysfunction. These investigations were sparked by findings that systemic administration of a synthetic analog of alpha-MSH, MT-II, causes penile erections in a variety of species, including humans. Several other melanocortinergic agents including HP-228, THIQ, and bremelanotide (PT-141) have since been shown to have erectogenic properties thought to be due to binding to melanocortin receptors in the central nervous system, particularly the hypothalamus. Bremelanotide, a nasally administered synthetic peptide, is the only melanocortinergic agent that has been clinically studied in both males and females. Data from Phase II clinical trials of bremelanotide support the use of melanocortin-based therapy for erectile dysfunction. Studies using animal models have demonstrated that pre-copulatory behaviors in female rats analogous to sexual arousal are evoked, and preliminary clinical data also suggest a role in promoting sexual desire and arousal in women. Based on bremelanotide clinical experience, administration of a melanocortin agonist is well tolerated and not associated the hypotension observed with phosphodiesterase-5 inhibitors currently used to treat erectile dysfunction. This review discusses investigations of melanocortin agonists for the treatment of sexual dysfunction with emphasis on proposed sites and mechanisms of action in the central nervous system that appear to be involved in melanocortinergic modulation of sexual function. Current research validates use of melanocortinergic agents for the treatment of both male and female sexual dysfunction.

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

“…Whereas sildenafil facilitated clitorial engorgement in women with sexual dysfunction [260], clinical efficacy of this drug in women with PD awaits further clarification [261]. Bremelanotide, a melanocortin receptor agonist, is applied to female sexual dysfunction, and is reported to be effective [262]. …”

Protective Effect of Alpha-Melanocyte-Stimulating Hormone (α-MSH) on the Recovery of Ischemia/Reperfusion (I/R)-Induced Retinal Damage in A Rat Model

“…Physiological functions of melanocyte-stimulating hormones include: stimulation of melanogenesis (Tsatmali et al 2002), regulation of appetite and energy balance (Morton et al 2006), sexual arousal, and erectile function (Shadiack et al 2007), along with a wide range of anti-inflammatory and protective effects, most notably protection from I/R injury (Lipton et al 1994). α-MSH is known to protect against ischemic damage of the brain (Forslin Aronsson et al 2006), kidney (Chiao et al 1997), and gastrointestinal tract (Zou et al 2003).…”

Metabolomics Reveals the Alteration of Metabolic Pathway by Alpha-Melanocyte-Stimulating Hormone in B16F10 Melanoma Cells

“…Melanogenesis can be stimulated by the ultraviolet or visible light-induced alpha-melanocyte-stimulating hormone (α-MSH) in melanocytes [ 1 ]. While α-MSH, an endogenous peptide hormone and neuropeptide of the melanocortin family, is well known for its physiological function of stimulation of melanin production, it also plays an important role in controlling appetite and energy balance [ 2 ], sexual activity [ 3 ] and ischemia and reperfusion-associated injury [ 4 ]. The effects of α-MSH to protect ischemic damage in various organs, such as brain [ 5 ] and gastrointestinal tract [ 6 ], have been reported.…”