Bremelanotide

What is bremelanotide?

Bremelanotide is a synthetic peptide of seven amino acids that acts as a melanocortin receptor agonist, a drug that switches on a family of brain receptors involved in appetite, pigmentation, and sexual response. Its FDA-approved form is sold as Vyleesi and treats low sexual desire in certain women.

It is given as a small subcutaneous (under-the-skin) self-injection in the thigh or abdomen. Its research name, still widely used online, is PT-141.

The history of bremelanotide

Bremelanotide came out of research on a tanning drug. It descends from Melanotan II, a melanocortin peptide developed from University of Arizona work on synthetic hormones that darken skin. During testing, Melanotan II was noticed to cause sexual arousal as a side effect, which led researchers to pursue the melanocortin pathway for sexual dysfunction, and the resulting compound, originally called PT-141, became bremelanotide.

It was developed by Palatin Technologies, tested first for erectile dysfunction and later for low desire in women, and the FDA approved it as Vyleesi in 2019. Its cousin from the same tanning research, afamelanotide, took a different path and became a treatment for a rare light-sensitivity disorder.

How does bremelanotide work?

Bremelanotide works in the brain rather than on the genitals. It activates melanocortin receptors, chiefly the MC4 receptor, in regions of the central nervous system that help regulate sexual desire. By stimulating this pathway it is thought to shift the balance of brain signals toward excitation, which can increase desire. This is a different mechanism from erectile dysfunction drugs such as sildenafil, which increase blood flow; bremelanotide targets desire itself.

It is used on demand rather than daily. In its pivotal RECONNECT trials, two phase 3 studies of 1,267 randomized premenopausal women with HSDD, bremelanotide produced a small but statistically significant gain on both outcomes over 24 weeks (P<.001 for both):

An independent reanalysis of the RECONNECT data judged the benefit statistically modest, and found little evidence that the desire and distress scales used as outcomes are valid in women with HSDD.

Is it FDA-approved?

Yes, in one specific form and use. The FDA approved bremelanotide as Vyleesi in 2019 for acquired, generalized hypoactive sexual desire disorder in premenopausal women. "Acquired" means the low desire developed after a period of normal function, and "generalized" means it is not limited to a certain partner or situation. Because the drug can briefly raise blood pressure, it is contraindicated in people with uncontrolled high blood pressure or known cardiovascular disease, and it is not approved for postmenopausal women or for men.

What is bremelanotide prescribed for?

Bremelanotide (Vyleesi) is prescribed for premenopausal women who have hypoactive sexual desire disorder, meaning persistent, distressing low sexual desire that is not better explained by another medical or psychiatric condition, relationship problems, or a medication. Its label advises stopping it when a woman reports no improvement. It is prescribed and monitored by a clinician.

What are the side effects?

The most common side effect is nausea, which was frequent in trials and sometimes required anti-nausea treatment. Other common effects include flushing, headache, vomiting, and injection-site reactions. Two effects deserve specific mention: Bremelanotide causes a transient rise in blood pressure and a brief drop in heart rate after each dose, which is why it is avoided in people with cardiovascular risk, and repeated use can cause focal hyperpigmentation, darkened patches of skin or gums, more likely with frequent dosing and in people with darker skin.

What about "PT-141" sold online?

Bremelanotide is sold widely online under its research name, PT-141, and this is not the same as the FDA-approved product. The only version the FDA has approved is Vyleesi, a prescription autoinjector for premenopausal women with HSDD. The PT-141 sold through "research chemical" vendors, and the vials and nasal sprays marketed for do-it-yourself use, are not FDA-approved medicines, and they are often labeled "not for human use" to sidestep regulation.

Several concerns follow from that:

• These products are not quality-controlled, so the actual identity, dose, purity, and sterility are not guaranteed, and contamination or incorrect dosing is a real risk.
• They are frequently marketed for uses the drug was never approved for, including in men and as a nasal spray, where it has not been tested to an approval standard.
• Because bremelanotide raises blood pressure and can affect heart rate, using an unregulated version without medical screening removes an important safety check.

Compounded bremelanotide, prescribed through some telehealth clinics, is a separate category: Compounded drugs are also not FDA-approved, and their quality depends heavily on the specific pharmacy. In short, the approved product is the only form that has been tested and regulated for safety, quality, and a defined use, while the versions sold online are neither approved nor quality-assured.

Sources: FDA prescribing information for Vyleesi (bremelanotide); the pivotal RECONNECT phase 3 trials in Obstetrics & Gynecology (Kingsberg et al., 2019, DOI: 10.1097/AOG.0000000000003500), indexed on PubMed; the manufacturer's (Palatin Technologies) approval announcement; and reference literature on bremelanotide's development from melanocortin research. This document is educational and does not constitute medical advice.