Bremelanotide (PT-141)

What Is Bremelanotide (PT-141)?

Bremelanotide, developed under the code PT-141, is a synthetic peptide analog of alpha-MSH that activates melanocortin receptors in the brain and is approved to treat low sexual desire in premenopausal women. It has high affinity for the melanocortin type 4 receptor, which is thought to be important for sexual function, giving it the potential to modulate brain pathways involved in sexual response.^[1]

In the United States it is approved for premenopausal women with acquired, generalized hypoactive sexual desire disorder, characterized by low sexual desire that causes marked distress or interpersonal difficulty.^[1] Clinical reviews describe it as one of two recently approved medications for HSDD, alongside flibanserin.^[2]

Bremelanotide belongs to a small group of FDA-approved melanocortin agonists that also includes afamelanotide, approved for erythropoietic protoporphyria, and setmelanotide, approved for certain genetic forms of obesity.^[3] It is closely related in structure to the unapproved research peptide Melanotan II.

Chemical Structure and Molecular Identity

Bremelanotide is a seven-residue cyclic peptide, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, closed by a lactam bond between the side chains of aspartic acid and lysine. PubChem (CID 9941379) lists the molecular formula C50H68N14O10 and a molecular weight of 1025.2 g/mol. The CAS number is 189691-06-3.

The ring encloses the His-D-Phe-Arg-Trp segment shared with alpha-MSH-derived melanocortin peptides. The N-terminus carries an acetylated norleucine, a non-standard amino acid, and position 4 is D-phenylalanine. Because of these features and the cyclic structure, its sequence cannot be written in standard one-letter code.

Bremelanotide and Melanotan II share the same cyclic backbone. The only difference is at the C-terminus: bremelanotide ends in a free carboxylic acid, whereas Melanotan II ends in an amide. That gives bremelanotide one more oxygen and one fewer nitrogen and hydrogen (C50H68N14O10 versus C50H69N15O9) and a molecular weight about one unit higher.

Comparison with Melanotan II

Names and synonyms

• Generic name: bremelanotide (INN and USAN)
• Development code: PT-141, PT141
• Chemical description: N-acetyl-L-norleucyl-L-alpha-aspartyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-lysine (2-7)-lactam

Research History and Development

Bremelanotide began as a nasal spray for erectile dysfunction and was later redeveloped for women with hypoactive sexual desire disorder, leading to US approval in 2019. A 2004 profile described PT-141 as a synthetically modified analog of the peptide PT-14, then in development as a nasal spray for erectile dysfunction and female sexual dysfunction. A phase IIb trial in men with erectile dysfunction had been completed in September 2003, and phase III trials were planned.^[4]

A randomized, double-blind, placebo-controlled study published in 2008 tested intranasal bremelanotide in men with erectile dysfunction who had not responded to sildenafil.^[5] Development subsequently shifted to women. Palatin Technologies sponsored the phase 3 clinical trials and later out-licensed exclusive North American rights to develop and commercialize the drug, including submission of the New Drug Application to the FDA.^[1]

The 2019 US approval for premenopausal women with acquired, generalized HSDD was the drug’s first regulatory approval.^[1] Since then, reviewers have examined its place among treatments for female sexual dysfunction and for low libido in specific populations, such as women with breast cancer receiving endocrine therapy.^[6][7]

Mechanisms Studied in Research

Bremelanotide works as a melanocortin receptor agonist, and its effects on sexual desire are attributed mainly to activation of the melanocortin-4 receptor in the central nervous system.^[1]

Melanocortin receptor activation

Melanocortin receptors serve functions ranging from skin pigmentation, appetite regulation, stress response and cognition to steroid synthesis, energy balance and immunomodulation.^[3] Bremelanotide’s high MC4R affinity is the property linked to its sexual-function effects.^[1]

Contrast with other HSDD treatments

Bremelanotide’s mechanism differs from that of flibanserin, the other approved HSDD medication: flibanserin acts as a serotonin and dopamine modulator, while bremelanotide acts as a melanocortin receptor agonist.^[7] Clinical reviewers frame HSDD within a dual-control model, in which multiple hormones and neurotransmitters likely balance excitation and inhibition of sexual desire, although a definitive physiology of the disorder is still unknown.^[2]

Diagnostic context

HSDD is defined by a deficiency of sexual thoughts, feelings or receptiveness to sexual stimulation that has persisted for at least six months, causes personal distress and is not due to another medical condition. It is the most commonly identified sexual problem among women, and nearly half of women in the United States report some problem with sexual function. Reviewers stress validated screening tools and a biopsychosocial assessment when evaluating it, since many providers do not routinely ask about sexual concerns.^[2]

Key Findings From Published Studies

Controlled trials and a 2026 meta-analysis show that bremelanotide improved measures of sexual desire, arousal and related distress in women, and an earlier trial reported benefit in men with erectile dysfunction who had not responded to sildenafil. Findings are summarized below by population.

Women with sexual desire and arousal disorders

• A 2026 systematic review and meta-analysis of 36 studies of female desire, arousal and orgasmic dysfunction (26 of them randomized controlled trials) found that bremelanotide improved the total Female Sexual Function Index score and its desire and arousal subscales, and reduced distress.^[6]
• In the same analysis, flibanserin improved total score and desire, and mindfulness-based cognitive behavioral therapy improved desire, arousal and orgasm; no studies directly compared therapy with medication.^[6]
• Clinical trials of bremelanotide excluded patients with breast cancer, so data in that population are lacking.^[7]

Men with erectile dysfunction

• In a randomized, double-blind, placebo-controlled trial of 342 men with erectile dysfunction who had not responded to sildenafil, positive clinical results were seen in 33.5% of the bremelanotide group versus 8.5% of the placebo group (p = 0.03).^[5]
• The bremelanotide group reported significantly greater intercourse satisfaction, but also had more drug-related adverse effects (p = 0.01). The authors called for further studies before drawing final conclusions.^[5]

Erectile dysfunction is not an approved indication for bremelanotide.

Because bremelanotide and Melanotan II differ by one C-terminal group, researchers typically confirm identity with mass spectrometry and HPLC certificates of analysis.

Because bremelanotide and Melanotan II differ by one C-terminal group, researchers typically confirm identity with mass spectrometry and HPLC certificates of analysis.

Regulatory and Research Status

Bremelanotide is an FDA-approved prescription drug for premenopausal women with acquired, generalized hypoactive sexual desire disorder; it is not approved for men or for erectile dysfunction.^[1][3] The approval covers a specific pharmaceutical product and indication.

Material labeled PT-141 and sold as a research peptide is chemically the same molecule but is not the approved drug product and has not been evaluated by regulators for identity, purity or sterility. Because PT-141 and Melanotan II differ by a single terminal group, mislabeling between the two would be difficult to detect without accurate mass spectrometry.

Open research questions include the drug’s effects in populations excluded from pivotal trials, such as women with breast cancer on endocrine therapy, how it compares directly with non-drug approaches, and whether the early erectile dysfunction findings would hold up with further study.^[7][6][5]