Abstract
Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile erection. While the CNS contains principally the MC3 and MC4 receptor subtypes, there is conflicting data as to which receptor mediates erection. Although the MC4R is emerging as the principle effector of MC induced erection, the role of the MC3R is poorly understood. Manipulation of each receptor subtype with newly synthesized receptor specific agonists and antagonists, as well as knockout mice, has elucidated their individual contributions. Novel data from our laboratories suggests that antagonism of forebrain MC3R may enhance melanocortin-induced erections. Furthermore, melanocortin agents may interact with better-studied systems such as oxytocinergic pathways at the hypothalamic, brainstem or spinal level. Current therapies for erectile dysfunction target end organ vascular tissue. Manipulation of MC receptors may provide an alternative, centrally mediated therapeutic approach for erectile and other sexual dysfunctions. The non-specific “ superpotent ” MC agonist, PT-141, which is the carboxylate derivative of MT-II, has reached phase II human trials. Through their centrally mediated activity, melanocortin agonists have potential to treat erectile dysfunction as well as possible applications to the unmet medical needs of decreased sexual motivation and loss of libido.
Keywords: hindbrain melanocortin signaling, npgi neurons, thiq, pt-141, erectogenic, melanotan-II
Current Topics in Medicinal Chemistry
Title: Melanocortin Receptors, Melanotropic Peptides and Penile Erection
Volume: 7 Issue: 11
Author(s): Hunter Wessells, Todd W. Vanderah, Victor J. Hruby, Preeti Balse-Srinivasan, Stephen H. King and Alexander V. Mayorov
Affiliation:
Keywords: hindbrain melanocortin signaling, npgi neurons, thiq, pt-141, erectogenic, melanotan-II
Abstract: Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile erection. While the CNS contains principally the MC3 and MC4 receptor subtypes, there is conflicting data as to which receptor mediates erection. Although the MC4R is emerging as the principle effector of MC induced erection, the role of the MC3R is poorly understood. Manipulation of each receptor subtype with newly synthesized receptor specific agonists and antagonists, as well as knockout mice, has elucidated their individual contributions. Novel data from our laboratories suggests that antagonism of forebrain MC3R may enhance melanocortin-induced erections. Furthermore, melanocortin agents may interact with better-studied systems such as oxytocinergic pathways at the hypothalamic, brainstem or spinal level. Current therapies for erectile dysfunction target end organ vascular tissue. Manipulation of MC receptors may provide an alternative, centrally mediated therapeutic approach for erectile and other sexual dysfunctions. The non-specific “ superpotent ” MC agonist, PT-141, which is the carboxylate derivative of MT-II, has reached phase II human trials. Through their centrally mediated activity, melanocortin agonists have potential to treat erectile dysfunction as well as possible applications to the unmet medical needs of decreased sexual motivation and loss of libido.
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Hunter Wessells , Todd W. Vanderah , Victor J. Hruby , Preeti Balse-Srinivasan , Stephen H. King and Alexander V. Mayorov , Melanocortin Receptors, Melanotropic Peptides and Penile Erection, Current Topics in Medicinal Chemistry 2007; 7 (11) . https://dx.doi.org/10.2174/1568026610707011111
DOI https://dx.doi.org/10.2174/1568026610707011111 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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