Compound research
PT-141: research overview
PT-141 (bremelanotide) is a synthetic peptide analogue of alpha-melanocyte-stimulating hormone (alpha-MSH), developed by Palatin Technologies and described as an analogue of melanotan II. It has been described as an agonist at melanocortin receptors, including MC3R and MC4R, and has been studied in rats, non-human primates and human clinical trials in the context of sexual function.1–5
Mechanism at a glance
- Melanocortin 4 receptor (MC4R)A 2019 review describes bremelanotide as having high affinity for MC4R, a receptor expressed mainly in the central nervous system.1, 5
- Melanocortin 3 receptor (MC3R)A second melanocortin receptor expressed mainly in the central nervous system, at which PT-141 has been described as an agonist.1
- Hypothalamic neuronsIncreased c-Fos labelling, a marker of neuronal activation, was reported in rat hypothalamic neurons; viral tracing from penile tissue labelled the same region.1
- Central melanocortin system (alpha-MSH signalling)PT-141 is an alpha-MSH analogue; a female rat study linked central melanocortin systems to sexual solicitation behaviour.2, 5
The receptor distribution and the rat findings point to a central site of action, although the female rat study referred to central melanocortin receptors in general without naming a specific subtype.1, 2
What it is
PT-141, also known as bremelanotide, is a synthetic peptide analogue of alpha-MSH. A 2006 review describes it as an analogue of melanotan II, a cyclic, truncated melanocortin peptide, and names Palatin Technologies as its developer. Palatin later granted AMAG Pharmaceuticals exclusive North American rights to develop and commercialise it.1, 3, 5
How it acts
PT-141 has been described as an agonist at melanocortin receptors, including MC3R and MC4R. These receptors are expressed mainly in the central nervous system. A 2019 review describes bremelanotide as having high affinity for MC4R.1, 5
Animal models
In rats and non-human primates, PT-141 was reported to produce penile erections. In rats, it was reported to increase c-Fos labelling, a marker of neuronal activation, in hypothalamic neurons. Viral tracing from penile tissue labelled neurons in the same region of the central nervous system. These findings are consistent with a central site of action.1
Female rat behaviour
In female rats, PT-141 was reported to increase solicitation behaviour selectively. Lordosis, pacing and other sexual behaviours were reported to be unaffected, and no general motor activation was seen. The authors suggested that central melanocortin systems take part in regulating female sexual desire.2
Research status
Early clinical studies examined erectile responses in healthy men and in men with erectile dysfunction. A 2006 review reported that PT-141 had been through phase 1/2 trials and was due to enter phase 3 trials. Later phase 3 trials enrolled women.1, 3, 4
Human trials
Two identical randomised, double-blind, placebo-controlled phase 3 trials, known as RECONNECT, enrolled premenopausal women with hypoactive sexual desire disorder (HSDD). They were funded by Palatin Technologies and AMAG Pharmaceuticals. The co-primary endpoints examined change in sexual desire and in distress related to low desire, measured by questionnaire.4
Regulatory context
The US Food and Drug Administration approved bremelanotide in 2019. The approval covers premenopausal women with acquired, generalised HSDD. A 2021 analysis critically discussed the trial outcomes and regulatory reasoning behind this approval and the earlier approval of flibanserin.5, 6
Published research at a glance
- Animal model
Sexual solicitation, lordosis, pacing and motor activity in female rats
- Review
Melanocortin receptor activity, hypothalamic c-Fos labelling and erectile responses in rats, non-human primates and men
- Review
Historical development of melanocortin peptides, including melanotan II and PT-141
- Clinical trial
Two randomised, placebo-controlled phase 3 trials in premenopausal women with HSDD; endpoints on sexual desire and related distress
- Review
Development milestones leading to the first US approval
- Review
Critical analysis of trial data and regulatory decisions for bremelanotide and flibanserin
Research status: The US Food and Drug Administration approved bremelanotide in 2019 for premenopausal women with acquired, generalised hypoactive sexual desire disorder.5, 6
Technical specifications
- Molecular formula
- C50H68N14O10
- Molecular weight
- 1025 Da
- CAS number
- 189691-06-3
References
- Molinoff PB, Shadiack AM, Earle D, et al. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences (2003). doi:10.1111/j.1749-6632.2003.tb03167.x
- Pfaus JG, Shadiack A, Van Soest T, et al. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proceedings of the National Academy of Sciences of the United States of America (2004). doi:10.1073/pnas.0400491101
- Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides (2006). doi:10.1016/j.peptides.2005.01.029
- Kingsberg SA, Clayton AH, Portman D, et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstetrics and Gynecology (2019). doi:10.1097/AOG.0000000000003500
- Dhillon S, Keam SJ. Bremelanotide: First Approval. Drugs (2019). doi:10.1007/s40265-019-01187-w
- Mintzes B, Tiefer L, Cosgrove L. Bremelanotide and flibanserin for low sexual desire in women: the fallacy of regulatory precedent. Drug and Therapeutics Bulletin (2021). doi:10.1136/dtb.2021.000020
Literature summary compiled on 15 October 2026.