PT-141: How a Quest for a Sunless Tan Led to a Desire Peptide

In the Arizona desert, scientists had a bold dream. They wanted a tan that did not need the sun.

One of their tanning peptides came with a surprise side effect. Years later, a cousin of it became a medicine for women with low sexual desire. That cousin is PT-141.

What it is

PT-141 is also called bremelanotide. It is a peptide, a short chain of building blocks called amino acids. Think of amino acids as beads and a peptide as a short bead bracelet. New to this? Start with what a peptide is.

PT-141 has just seven beads. Six of them are joined in a closed loop, like a tiny ring.

It copies part of a natural hormone called alpha-MSH. This hormone tells skin to make more color.

The story starts in 1980 at the University of Arizona. The team built a longer-lasting copy of alpha-MSH. They tested it on frog skin, which turns darker when the hormone shows up.

They saw an exciting idea in it: a tan without the sun. A tan like that might help shield skin from cancer. In 1991, the team showed their peptide could darken the skin of 28 men, no sunbathing needed.

Next came a smaller, ring-shaped cousin called Melanotan II. In 1996, the team tested it in three healthy men. Two got darker skin. The study also noted a side effect nobody was aiming for: spontaneous arousal.

That happy accident changed the plan. PT-141 was later made from Melanotan II, this time to study sexual health.

What it does in the body

PT-141 works on melanocortin receptors. A receptor is a lock on a cell, and the peptide is the key.

Two of these locks matter most. One sits on skin pigment cells. The other is found on nerve cells in many parts of the brain.

Desire runs on a balance of "go" and "stop" signals in the brain. Experts think low desire can happen when the "stop" side wins. Melanocortins are linked to the "go" side.

So PT-141 is aimed at the brain. Exactly how is still being explored.

What scientists have found

In cells: In lab tests, PT-141 turned on several kinds of melanocortin locks. It was most powerful at the lock on skin pigment cells. That is the lock that darkens skin.

In animals: In a 2004 study, female rats got PT-141. They made more of the moves female rats use to invite a mate, like little hops and darts.

Other mating behaviors stayed the same. The authors said this pointed to brain melanocortins as a key part of female desire.

In people: The big tests were two trials called RECONNECT. They ran from 2015 to 2016 with 1,267 premenopausal women. All had low sexual desire that caused them distress. Doctors call this hypoactive sexual desire disorder, or HSDD.

Half got PT-141 and half got a placebo, a dummy shot, for 24 weeks. Women rated how often and how strongly they felt desire. They also rated how often low desire bothered them.

In both trials, desire rose more and distress fell more with PT-141 than with placebo. On a desire scale of about 1 to 6, scores rose about half a point with PT-141. With placebo, they rose about a fifth of a point.

Most side effects were mild or moderate. The most common was nausea, reported by 40% of women on PT-141 versus about 1% on placebo. Flushing and headache were also common. About 1% saw darker patches of skin, an echo of the tanning story.

In a fascinating 2022 study, 31 women with HSDD had brain scans. With PT-141, desire rose for up to 24 hours compared with placebo. Their brains also responded differently to sexual images.

Where it stands

PT-141 has been FDA-approved since 2019, as Vyleesi, for HSDD in premenopausal women only.

That is quite a journey, from a frog-skin tanning test to an approved medicine. Next, researchers want to learn exactly how it works in the brain. Another hormone peptide with strong brain ties is kisspeptin.

The bottom line

• PT-141 is a seven-bead, ring-shaped peptide born from a sunless-tanning project and a surprise discovery.
• In two large trials in women with HSDD, desire rose more than with placebo. In 2019, it became an FDA-approved medicine.
• It works on melanocortin locks, including one on brain cells, and brain scans now offer an exciting look at how.