# PT-141 (Bremelanotide): The Melanocortin Research Record > PT-141 (bremelanotide) is FDA-approved for HSDD in premenopausal women. 43 clinical trials, 3,500 subjects, one central mechanism. Indexed here from the primary literature. ## What Is PT-141? PT-141 is a cyclic heptapeptide — seven amino acids arranged in a ring — also known by its international nonproprietary name, bremelanotide. Molecular formula C50H68N14O10, molecular weight 1025.2 Da, CAS 189691-06-3. It is a synthetic analogue of alpha-melanocyte-stimulating hormone (alpha-MSH), derived from melanotan II by removal of the C-terminal amide. PT-141 is not a vascular drug. It does not act on smooth muscle or change blood flow directly. Instead, it binds to melanocortin receptors — primarily MC3R and MC4R — in the hypothalamus and limbic system, activating central neural pathways associated with sexual desire and arousal. That central mechanism is what distinguishes it from every prior approach to sexual dysfunction pharmacology. Bremelanotide received FDA approval in June 2019 under the trade name Vyleesi for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. The approval was based on two identically designed Phase 3 randomized controlled trials, the RECONNECT program, in which bremelanotide at 1.75 mg subcutaneous demonstrated statistically significant improvements in desire scores and sexual distress measures versus placebo [5, 6]. This site covers the published research on PT-141 and bremelanotide: the mechanism, the clinical trial record, the pharmacokinetics, the side-effect profile, and the open questions. It does not sell, recommend, or prescribe. ## PT-141: A Synthetic Melanocortin Peptide What sets PT-141 apart from earlier sexual-dysfunction compounds is its point of action: the brain, not the genitals. Sildenafil and related PDE-5 inhibitors act peripherally — they prevent the breakdown of cyclic GMP in vascular smooth muscle, increasing blood flow to erectile tissue. PT-141 acts upstream. It targets MC4R in the medial preoptic area (mPOA) of the hypothalamus, a region critical for sexual motivation in both males and females, and enhances presynaptic dopamine release [10, 15]. The result is a compound that addresses desire initiation — not just the vascular mechanics of sexual response. In rat models, peripheral or direct mPOA infusion of bremelanotide selectively increased solicitation (appetitive) sexual behaviors without affecting consummatory behaviors or locomotion, demonstrating the behavioral specificity of the MC4R pathway [10]. In human neuroimaging at 1.75 mg SC, bremelanotide enhanced cerebellar and supplementary motor area activity during erotic stimulus processing, reduced secondary somatosensory cortex activity (less self-monitoring), and enhanced amygdala-insula functional connectivity — consistent with top-down inhibition theory of HSDD pathophysiology [17]. PT-141's cyclic structure confers greater metabolic stability than linear melanocortin peptides. It binds MC4R with high affinity but is non-selective — it also activates MC3R (secondary pathway) and at higher doses MC1R, the receptor governing melanogenesis, which underlies the hyperpigmentation adverse event seen at high-frequency dosing [9]. ## What Does PT-141 Do? PT-141 (bremelanotide) is a synthetic analogue of alpha-MSH that acts as an agonist at MC3R and MC4R receptors in the central nervous system, activating neural pathways associated with sexual arousal and desire. The evidence base now spans 43 clinical studies across approximately 3,500 subjects [9]. In premenopausal women with HSDD, the RECONNECT Phase 3 program demonstrated statistically significant increases in satisfying sexual events per month and reductions in sexual distress scores (FSDS-DAO) versus placebo, with response rates approximately 58% bremelanotide versus 36% placebo [5]. A 52-week open-label extension showed sustained efficacy with no new safety signals through 76 weeks of total exposure [14]. In men, Phase 2 trials showed PT-141 produced dose-dependent erectile responses in healthy subjects and in men who did not respond adequately to sildenafil, at intranasal doses above 7 mg and at subcutaneous doses of 4–6 mg [1, 2]. The male indication has not progressed to Phase 3; it is not FDA-approved for this use. ## PT-141 Regulatory Status Bremelanotide received FDA approval on June 21, 2019 (NDA 210557) as Vyleesi — a 1.75 mg SC auto-injector for treatment of acquired, generalized HSDD in premenopausal women. The FDA-labeled dose is one 1.75 mg subcutaneous injection administered at least 45 minutes before anticipated sexual activity, with a maximum of one dose per 24 hours and eight doses per month. Recommended discontinuation after 8 weeks in the absence of benefit [6]. The drug is contraindicated in subjects with uncontrolled hypertension or known cardiovascular disease, due to transient blood pressure effects documented in the clinical program [8]. Post-menopausal women and men are not approved populations. ## What Is PT-141 Used for in Research? Research has focused on two primary areas: (1) sexual desire disorders in both sexes — particularly HSDD in premenopausal women (the approved indication) and erectile dysfunction in men (Phase 2 data, not approved) — and (2) the central melanocortin signaling pathway as a pharmacological target for CNS-mediated arousal and desire. A secondary research area, emerging from Phase 1 data, is the compound's effect on caloric intake and body weight via the same MC4R satiety circuits [19]. The overlap between the sexual-desire and metabolic pathways at MC4R is an active area of mechanistic research [18]. ## References [1] Diamond LE, et al. Double-blind, placebo-controlled evaluation of intranasal PT-141. Int J Impotence Research. 2004. https://pubmed.ncbi.nlm.nih.gov/14963471/ [2] Rosen RC, et al. Evaluation of subcutaneous PT-141. Int J Impotence Research. 2004. https://pubmed.ncbi.nlm.nih.gov/14999221/ [5] Simon JA, et al. RECONNECT Phase 3 subgroup analyses. Journal of Women's Health. 2022. https://pubmed.ncbi.nlm.nih.gov/35230162/ [6] Mayer D, Lynch SE. Bremelanotide: New Drug Approved for HSDD. Annals of Pharmacotherapy. 2020. https://pubmed.ncbi.nlm.nih.gov/31893927/ [8] White WB, et al. Ambulatory blood pressure monitoring for bremelanotide. Journal of Hypertension. 2017. https://pubmed.ncbi.nlm.nih.gov/27977473/ [9] Clayton AH, et al. Safety Profile of Bremelanotide. Journal of Women's Health. 2022. https://pubmed.ncbi.nlm.nih.gov/35147466/ [10] Pfaus J, Giuliano F, Gelez H. Bremelanotide: preclinical CNS effects. Journal of Sexual Medicine. 2007. https://pubmed.ncbi.nlm.nih.gov/17958619/ [14] Simon JA, et al. Long-Term Safety and Efficacy of Bremelanotide. Obstetrics and Gynecology. 2019. https://pubmed.ncbi.nlm.nih.gov/31599847/ [15] Pfaus JG, et al. Neurobiology of bremelanotide for HSDD. CNS Spectrums. 2022. https://pubmed.ncbi.nlm.nih.gov/33455598/ [17] Thurston L, et al. MC4R agonism enhances sexual brain processing in women with HSDD. JCI. 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9525110/ [18] Semple EA, et al. MC4R signaling in Sim1 neurons permits sexual receptivity. Frontiers in Endocrinology. 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10080118/ [19] Spana C, Jordan R, Fischkoff S. Effect of bremelanotide on body weight. Diabetes Obesity Metabolism. 2022. https://pubmed.ncbi.nlm.nih.gov/35170192/ --- Coin-operated reading room for the bremelanotide literature — every trial catalogued, no clinical service rendered.