PT-141

PT-141, now known as bremelanotide (Vyleesi), is a synthetic peptide analogue of the neuropeptide hormone alpha melanocyte-stimulating hormone (alpha-MSH) with high affinity for the melanocortin type 4 receptor. ^[1] It was approved in the USA in 2019 for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), and is a self-administered, on-demand subcutaneous therapy. ^{[1] [2]}

Bremelanotide is a melanocortin receptor agonist that nonselectively activates several receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. ^[3] Animal studies suggest bremelanotide affects female sexual desire by activating presynaptic MC4Rs on neurons in the medial preoptic area of the hypothalamus, leading to increased release of dopamine, an excitatory neurotransmitter that increases sexual desire. ^[3]

Bremelanotide is the second FDA-approved medication for HSDD, a disorder estimated to affect approximately 10% of women in the United States. ^{[3] [4]} In Phase 3 trials bremelanotide demonstrated a significant improvement in sexual desire and a significant decrease in distress related to lack of desire, though the overall clinical benefit appears to be modest. ^{[4] [5]} The recommended dose is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 minutes before sexual activity, with no more than one dose in 24 hours and no more than eight doses per month. ^{[6] [4]} A critical appraisal noted that in clinical trials bremelanotide led to no additional enjoyable sexual experiences on average, and a re-analysis of the Phase III trials found participants substantially preferred placebo, suggesting the drug is generally not useful. ^{[7] [8]}

The most common adverse effects of bremelanotide are nausea (39.9%), facial flushing (20.4%), and headache (11%). ^[4] A re-analysis of the Phase III trials found that adverse event-induced study discontinuation was substantially higher on bremelanotide than placebo (odds ratio 11.98). ^[8]