PT-141

PT-141, whose generic name is bremelanotide, is a lab made peptide, meaning a short chain of the small building blocks that proteins are made from, closed into a ring. It is an altered copy of one of the body's own signals, called alpha melanocyte stimulating hormone. Unlike almost everything else in this reference it is an approved medicine: the United States Food and Drug Administration cleared it on 21 June 2019 under the brand name Vyleesi, for women who have not yet been through the menopause and who have lost sexual desire in a way that distresses them. That is the entire approval, and I found no European Medicines Agency authorisation under either name, so the American one is the only one that could be confirmed. Where the molecule sits in relation to melanotan II, the tanning peptide, is genuinely unsettled in print, and this entry does not tidy it up. Hadley and Dorr, writing in 2006, call PT-141 an analogue of melanotan II, meaning a separate molecule built to resemble it. Alwaal, Al-Mannie and Carrier, writing in 2011, call it an active metabolite of melanotan II, meaning something the body turns melanotan II into. Both are peer reviewed, and the two words do not mean the same thing, because a metabolite inherits a share of its parent's story and an analogue does not. The two molecules differ at the tail end, where this one carries a hydroxyl group in place of an amide.

It acts in the brain and spinal cord rather than in the sexual organs themselves. It switches on a family of docking points on cells called melanocortin receptors, and the two it is usually credited with, the third and the fourth of them, sit mainly in the central nervous system rather than in the genital tissue. The approved label is blunter than that: the drug turns the whole family on without picking between them, most strongly at the first, then the fourth, the third, the fifth and the second, and at the amounts actually given the two that matter are the first and the fourth. The first one is the receptor that controls skin pigment, which is why darkened patches of skin appear in the safety record. What moved in the trials was not a physical measurement but a score on a questionnaire about desire.

Inside the approval, it is prescribed to women who have not been through the menopause, for low sexual desire that distresses them. Outside it, men buy it. Every male measurement in the published literature is a measurement of erection, the approved use in women is about desire, and no study bridges them. It is also sold for sexual performance in general, which the approved label names in its Limitations of Use as something the drug is not indicated for, in the same two lines that name men and women past the menopause. That is what people take it for, not what has been shown in them.

The costly mistake is reading the approval as covering the person who bought it. The 1.75 mg figure is not a male number at all. It is the dose approved for premenopausal women, itself the top of three amounts, 0.75, 1.25 and 1.75 mg, compared in 327 premenopausal women in an earlier trial, and it was lifted off a label whose Limitations of Use name men as a group the drug is not indicated for. No male dose-finding study supports it, and I could not find a published trial of any design that has given a man that dose. The second mistake follows the first, which is assuming the thing being bought is large. In the trials, desire rose 0.35 points on a questionnaire and the distress item fell 0.33 points against the dummy injections, the number of satisfying sexual events did not differ significantly between the groups, and in the 52 week extension, where the drug was free and nobody was on a dummy, 684 women enrolled and 272 finished. The third is melanotan II, a separate molecule whose harm reports do not carry across, and which the published sources cannot agree is either this compound's parent or merely its lookalike.

In the phase 3 trials the side effects were not subtle. Nausea occurred in 40.0 percent of the women given bremelanotide against 1.3 percent on the dummy injections, flushing in 20.3 percent against 0.3 percent, reactions where the needle went in in 13.2 percent against 8.4 percent, and headache in 11.3 percent against 1.9 percent. Nausea was the most common reason people stopped, across a pooled safety review covering 3,500 subjects in 43 completed studies, in which there were no deaths. Then the skin, which is the first receptor coming back. Patches of darkened pigment appeared in about 1 percent of patients dosed up to eight times a month, and in 38 percent of patients given the drug every day for 8 days. It was more likely in patients with dark skin, and the label states that resolution was not confirmed in all patients, so what drives that jump is how often the drug is taken rather than how much. On the heart and circulation, blood pressure rose transiently by at most 6 millimetres of mercury on the upper number and 3 on the lower, with heart rate falling by up to 5 beats a minute, usually back to starting levels within 12 hours. The label rules the drug out entirely for anyone with uncontrolled high blood pressure or known heart or blood vessel disease.