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Molecular Formula | C₅₀H₆₈N₁₄O₁₀ |
CAS Number | 189691-06-3 |
Molar Mass | 1025.18 g/mol |
Amino Acid Sequence | Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-OH |
PubChem CID | 9941379 |
Primary Research Area |
Sexual Desire/Arousal Enhancement Hypoactive Sexual Desire Disorder (HSDD) Sexual Dysfunction (men & women) Melanocortin Receptor Agonism (MC3R, MC4R) Central Nervous System (CNS) Modulation |
Research Summary | Description |
---|---|
Bremelanotide for the treatment of hypoactive sexual desire disorder: Two randomized phase 3 trials |
Summary: These were two identical Phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT studies) evaluating bremelanotide 1.75 mg subcutaneously for premenopausal women with HSDD. Bremelanotide significantly increased sexual desire and reduced distress compared to placebo. Common adverse events included nausea, flushing, and headache. Citation: Clayton, A. H., Althof, S. E., Kingsberg, S., DeRogatis, L. R., Kroll, R., Portman, D., DeRogatis, L. R.,... & Simon, J. A. (2019). Bremelanotide for the treatment of hypoactive sexual desire disorder: Two randomized phase 3 trials. Obstetrics & Gynecology, 133(4), 755-765. |
Phase 2b, randomized, double-blind, placebo-controlled, dose-finding trial |
Summary: This trial involved 397 premenopausal women with HSDD or female sexual arousal disorder. Self-administered subcutaneous bremelanotide was taken as needed for up to 12 weeks. It showed dose-responsive improvements in desire, arousal, and associated distress with self-administered subcutaneous bremelanotide, leading to the selection of the 1.75 mg dose for further development. Citation: Clayton, A. H., Althof, S. E., Kingsberg, S., DeRogatis, L. R., Kroll, R., Portman, D., DeRogatis, L. R.,... & Simon, J. A. (2019). Bremelanotide for the treatment of hypoactive sexual desire disorder: Two randomized phase 3 trials. Obstetrics & Gynecology, 133(4), 755-765. |
PT-141 (Bremelanotide) for sexual dysfunction: clinical guide for physicians |
Summary: This article highlights that PT-141 activates melanocortin receptors MC3R and MC4R primarily within the hypothalamus, modulating pathways associated with sexual arousal, libido, and sexual satisfaction through central nervous system signaling rather than peripheral vasodilation. Citation: Enavvi. (n.d.). PT-141 (Bremelanotide) for Sexual Dysfunction: Clinical Guide for Physicians. |
PT-141: a melanocortin agonist for the treatment of sexual dysfunction |
Summary: This study investigated PT-141's effects in rats, nonhuman primates, and human clinical studies. It showed that PT-141 induced penile erections in animals and a rapid, dose-dependent increase in erectile activity in healthy men and those with erectile dysfunction. Citation: Molinoff, P. B., Shadiack, A. M., Earle, D., Diamond, L. E., & Quon, C. Y. (2003). PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences, 994(1), 96-102. |
Melanocortin-4 receptor agonism improves sexual brain processing in women with low sexual desire |
Summary: This clinical study investigated the effects of a melanocortin-4 receptor (MC4R) agonist (like bremelanotide) on brain activity related to sexual desire in premenopausal women with hypoactive sexual desire disorder (HSDD). Using functional MRI, psychometric measures, and hormonal analyses, the researchers found that MC4R agonism significantly increased sexual desire and enhanced brain regions involved in sexual processing (e.g., cerebellum, supplementary motor area, amygdala-insula connectivity) in response to erotic stimuli, compared to placebo. It also deactivated the secondary somatosensory cortex. APA Citation: Walpole, L., Ghosal, S., Koundal, S., Dhillo, W. S., & Le Roux, C. W. (2021). Melanocortin-4 receptor agonism improves sexual brain processing in women with low sexual desire. Endocrine Abstracts, 77, OC1.1. |
Melanocortins in the treatment of male and female sexual dysfunction |
Summary: This review article provides a comprehensive overview of the role of melanocortinergic agents, including PT-141 (bremelanotide), in treating sexual dysfunction in both men and women. It highlights that the therapeutic investigations were sparked by the accidental discovery of penile erections caused by a synthetic alpha-MSH analog (Melanotan II). The review discusses how bremelanotide, specifically, has been clinically studied and shows promise for erectile dysfunction in men and promoting sexual desire and arousal in women by acting on central nervous system melanocortin receptors, particularly in the hypothalamus. It also notes that bremelanotide administration is generally well-tolerated and not associated with the hypotension seen with PDE-5 inhibitors. APA Citation: Diamond, L. E., & Earle, D. C. (2007). Melanocortins in the treatment of male and female sexual dysfunction. Current Topics in Medicinal Chemistry, 7(11), 1081-1087. |
Summary: These were two identical Phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT studies) evaluating bremelanotide 1.75 mg subcutaneously for premenopausal women with HSDD. Bremelanotide significantly increased sexual desire and reduced distress compared to placebo. Common adverse events included nausea, flushing, and headache.
Citation: Clayton, A. H., Althof, S. E., Kingsberg, S., DeRogatis, L. R., Kroll, R., Portman, D., DeRogatis, L. R.,... & Simon, J. A. (2019). Bremelanotide for the treatment of hypoactive sexual desire disorder: Two randomized phase 3 trials. Obstetrics & Gynecology, 133(4), 755-765.
Summary: This trial involved 397 premenopausal women with HSDD or female sexual arousal disorder. Self-administered subcutaneous bremelanotide was taken as needed for up to 12 weeks. It showed dose-responsive improvements in desire, arousal, and associated distress with self-administered subcutaneous bremelanotide, leading to the selection of the 1.75 mg dose for further development.
Citation: Clayton, A. H., Althof, S. E., Kingsberg, S., DeRogatis, L. R., Kroll, R., Portman, D., DeRogatis, L. R.,... & Simon, J. A. (2019). Bremelanotide for the treatment of hypoactive sexual desire disorder: Two randomized phase 3 trials. Obstetrics & Gynecology, 133(4), 755-765.
Summary: This article highlights that PT-141 activates melanocortin receptors MC3R and MC4R primarily within the hypothalamus, modulating pathways associated with sexual arousal, libido, and sexual satisfaction through central nervous system signaling rather than peripheral vasodilation.
Citation: Enavvi. (n.d.). PT-141 (Bremelanotide) for Sexual Dysfunction: Clinical Guide for Physicians.
Summary: This study investigated PT-141's effects in rats, nonhuman primates, and human clinical studies. It showed that PT-141 induced penile erections in animals and a rapid, dose-dependent increase in erectile activity in healthy men and those with erectile dysfunction.
Citation: Molinoff, P. B., Shadiack, A. M., Earle, D., Diamond, L. E., & Quon, C. Y. (2003). PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences, 994(1), 96-102.
Summary: This clinical study investigated the effects of a melanocortin-4 receptor (MC4R) agonist (like bremelanotide) on brain activity related to sexual desire in premenopausal women with hypoactive sexual desire disorder (HSDD). Using functional MRI, psychometric measures, and hormonal analyses, the researchers found that MC4R agonism significantly increased sexual desire and enhanced brain regions involved in sexual processing (e.g., cerebellum, supplementary motor area, amygdala-insula connectivity) in response to erotic stimuli, compared to placebo. It also deactivated the secondary somatosensory cortex.
APA Citation:
Walpole, L., Ghosal, S., Koundal, S., Dhillo, W. S., & Le Roux, C. W. (2021). Melanocortin-4 receptor agonism improves sexual brain processing in women with low sexual desire. Endocrine Abstracts, 77, OC1.1.
Summary: This review article provides a comprehensive overview of the role of melanocortinergic agents, including PT-141 (bremelanotide), in treating sexual dysfunction in both men and women. It highlights that the therapeutic investigations were sparked by the accidental discovery of penile erections caused by a synthetic alpha-MSH analog (Melanotan II). The review discusses how bremelanotide, specifically, has been clinically studied and shows promise for erectile dysfunction in men and promoting sexual desire and arousal in women by acting on central nervous system melanocortin receptors, particularly in the hypothalamus. It also notes that bremelanotide administration is generally well-tolerated and not associated with the hypotension seen with PDE-5 inhibitors.
APA Citation:
Diamond, L. E., & Earle, D. C. (2007). Melanocortins in the treatment of male and female sexual dysfunction. Current Topics in Medicinal Chemistry, 7(11), 1081-1087.
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