PT-141 (bremelanotide)
PT-141, or bremelanotide, is a cyclic heptapeptide melanocortin receptor agonist derived from melanotan II. It was FDA-approved in 2019 as Vyleesi for hypoactive sexual desire disorder in premenopausal women.
Overview
Bremelanotide was developed from melanotan II, a synthetic melanocortin analogue created at the University of Arizona. Researchers noticed that melanotan II affected sexual arousal in early human studies, and bremelanotide was developed as a related compound focused on that effect. Development was carried out by Palatin Technologies, and the product was later licensed for commercialization. Its approved labeling defines the population in which its effects have been established.
In 2019 the FDA approved bremelanotide as Vyleesi for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) that is not due to a medical or psychiatric condition, relationship problems or medication effects. Approval was based on two phase 3 trials known as the RECONNECT studies. Bremelanotide acts in the central nervous system rather than on blood flow, which distinguishes it from phosphodiesterase-5 inhibitors used for erectile dysfunction.
Compare: PT-141 vs Melanotan II.
Structure
Bremelanotide is a cyclic heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. It is cyclized through a lactam bridge between the side chains of aspartic acid and lysine, contains norleucine (Nle) and D-phenylalanine, and is N-terminally acetylated. It differs from melanotan II at the C-terminus, which is a free acid in bremelanotide and an amide in melanotan II. The His-D-Phe-Arg-Trp core is the conserved melanocortin pharmacophore. The tryptophan is oxidation-prone.
Mechanism
Bremelanotide is an agonist at melanocortin receptors, with its sexual-function effects attributed mainly to activation of the melanocortin-4 receptor (MC4R) in the brain. MC4R signaling in the hypothalamus is involved in pathways linked to sexual motivation, and in animal studies activation is associated with changes in dopamine release in regions related to reward. Bremelanotide is not fully selective; activity at the MC1R on melanocytes explains reports of skin darkening, and activity at other subtypes may contribute to other effects.
Research
RECONNECT phase 3 trials
The RECONNECT program consisted of two randomized, placebo-controlled phase 3 trials in premenopausal women with HSDD. Both trials reported statistically significant improvements versus placebo on co-primary endpoints measuring sexual desire and the distress associated with low desire. The size of the differences was modest. These trials formed the basis for the 2019 FDA approval and were published in 2019. Many participants in both groups continued in open-label extension studies.
Safety findings in trials
The most frequently reported adverse effect in clinical trials was nausea. Trials also documented transient increases in blood pressure and decreases in heart rate after dosing, and focal skin hyperpigmentation was reported in some participants, consistent with activity at MC1R. These findings are reflected in the approved product labeling, which includes cardiovascular-related limitations. Safety in other populations has not been established.
Earlier and other research
Before the HSDD program, bremelanotide was studied in men with erectile dysfunction and in other formulations, but development in those areas did not lead to approval. Animal research has examined central melanocortin pathways in sexual behavior. Outside the approved indication, evidence remains investigational. Research on central melanocortin signaling in sexual function continues in animal models, and bremelanotide is often used as a reference compound in that work. Effects in men and in postmenopausal women have not been established in approval-level trials.
Regulatory status
Bremelanotide (PT-141) was approved by the FDA in 2019 as Vyleesi for acquired, generalized hypoactive sexual desire disorder in premenopausal women. It is not FDA-approved for men or for other uses. Status in other countries should be checked locally. For sport, check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A bremelanotide certificate of analysis should confirm identity by mass spectrometry against the expected mass shown on this page and report HPLC purity. Important pitfalls include distinguishing bremelanotide from melanotan II, which differs only by a C-terminal amide versus acid (about 1 Da); high-resolution MS and a reference standard are needed to separate them reliably. Incomplete cyclization gives a linear species with a +18 Da mass. Tryptophan oxidation and D-Phe epimerization should also be considered. Salt form and net peptide content should be reported.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized bremelanotide sealed at -20 °C, protected from light and moisture. The tryptophan residue is light- and oxidation-sensitive, so use amber vials or light shielding. The cyclic lactam structure improves stability compared with linear peptides, but solutions should still be aliquoted, kept cold and not repeatedly freeze-thawed.
Download the PT-141 (bremelanotide) data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention PT-141 (bremelanotide) in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
Is PT-141 FDA approved?
Yes, for a specific indication. Bremelanotide, also known as PT-141, was approved by the FDA in 2019 as Vyleesi for premenopausal women with acquired, generalized hypoactive sexual desire disorder. It is not approved for men or for other conditions. Approval was based on two phase 3 trials called RECONNECT.
What is the difference between PT-141 and melanotan II?
Bremelanotide (PT-141) was developed from melanotan II, and the two share the same cyclic heptapeptide core. The structural difference is at the C-terminus: bremelanotide ends in a free carboxylic acid, while melanotan II ends in an amide. Bremelanotide went through clinical development and was approved for HSDD; melanotan II has not been approved anywhere.
How is bremelanotide different from PDE5 inhibitors?
Phosphodiesterase-5 inhibitors such as sildenafil act on blood flow in peripheral tissue and are approved for erectile dysfunction. Bremelanotide acts on melanocortin receptors in the brain, mainly MC4R, and is approved for a disorder of sexual desire rather than of physical arousal. The two classes therefore have different targets, mechanisms and approved uses.
Related compounds
- Melanotan II
Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that activates several melanocortin receptors. It is not approved as a medicine anywhere, and regulators have warned about unlicensed tanning products.
- Kisspeptin-10
Kisspeptin-10 is the C-terminal decapeptide of kisspeptin, the product of the KISS1 gene. It activates the kisspeptin receptor (KISS1R, also called GPR54) and is studied as a regulator of gonadotropin-releasing hormone and reproductive hormones.
- Oxytocin
Oxytocin is a nine-amino-acid peptide hormone made in the hypothalamus and released from the posterior pituitary, with a disulfide-bridged ring structure. It regulates uterine contraction and milk ejection, and synthetic oxytocin (Pitocin) is FDA-approved.
References
- Kingsberg SA, Clayton AH, Portman D, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol. 2019. Find on PubMed
- PubMed: all indexed literature on PT-141 (bremelanotide)
- ClinicalTrials.gov: registered studies mentioning PT-141 (bremelanotide)
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