Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies

Abstract

The data available at present have facilitated our understanding of how the melanocortin pathway regulates both the male and female sexual functions. Indeed the data warrant further investigation to demonstrate the impact of the activation of MCRs by specific agonists on penile erection and female arousal and orgasm function.

An in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers

“…The use of 7 to decrease food intake in mice demonstrates its utility as a probe for metabolic diseases such as obesity. Additionally, the current study's finding that melanocortin bivalent are well tolerated and functionally active in vivo indicates that they will also be useful probes for other disease states in which the melanocortin system plays a role including Alzheimer's disease, 18-19 sexual function, 3, 26 and social disorders. 27-28 …”

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016

“…Melanocortin ligands have utilized in basic and clinical research in both males and females for treating sexual function disorders [170]. Although the MTII derivative bremelanotide has shown efficacy in both males and females, bremelanotide is currently only in clinical trials for female sexual desire disorder (For structure, see Figure 6 below) [170-173].…”

“…Although the MTII derivative bremelanotide has shown efficacy in both males and females, bremelanotide is currently only in clinical trials for female sexual desire disorder (For structure, see Figure 6 below) [170-173]. To the authors knowledge, the decision to focus on females for therapeutic development is the first clinical attempt in utilizing sex differences of melanocortin ligands.…”

“…To the authors knowledge, the decision to focus on females for therapeutic development is the first clinical attempt in utilizing sex differences of melanocortin ligands. The differential effects of melanocortin ligands on sexual function in males and females has been extensively reviewed [170, 171, 174], and will not be discussed in further detail herein.…”

A Direct in Vivo Comparison of the Melanocortin Monovalent Agonist Ac-His-DPhe-Arg-Trp-NH2 versus the Bivalent Agonist Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2: A Bivalent Advantage

“…21–36 Many of these studies focus on the development of bivalent ligands for their use as high affinity imaging tools or targeting agents for melanoma. 24–36 Given that chemical probes for the five melanocortin receptor subtypes (MC1-5R) have been utilized to study several diseases and disorders including Alzheimer’s disease, 44–46 sexual function disorders, 47, 48 social disorders, 49, 50 cachexia, 51–56 and obesity; 21, 57, 58 it is of interest to study the biological functions of bivalent ligands targeting these receptors. The limited reports of the in vitro functional effects of melanocortin homobivalent have all shown increased functional potency (up to 16-fold).…”