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Doctor PT-141

Sexual desire, discussed at full length.

PT-141 reading list

The clinical trials are a good place to start. The label, mechanism studies and historical papers pull the conversation in different directions.

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Clinical studies

The RECONNECT trial report contains the randomized comparisons of desire and distress. The longer extension follows continued treatment and tolerability. The prescribing information supplies the approved indication, contraindications and pharmacokinetic details. For the development and approval context, there is also the first-approval review.

I’d put these together before approaching the more elaborate accounts of how the drug might work. The practical question about benefit and burden is already visible in them.

Behavior and brain activity

The female-rat solicitation experiment, women’s brain-imaging study and female Syrian hamster reward experiment investigate different aspects of sexual behavior. The neurobiology review draws the proposed mechanisms together; the female-mouse receptor study concerns a specific cellular pathway.

For another angle on pleasure, I’d reopen the hamster paper when a broad claim sounds too settled. Its negative result is useful, within the limits of its animal model.

Safety and development history

The ambulatory blood-pressure paper and pooled safety analysis address measured adverse effects. The LiverTox entry covers liver concerns. The forensic study and melanotan-II toxicity report concern unregulated material and a related compound, respectively.

For the earlier route through tanning and sexual-function research, the historical review and 2004 development profile are particularly useful. The full reading list follows, including later reviews and broader background papers.

  1. Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003;994:96-102. ↗
  2. Pfaus J, Shadiack A, Van Soest T, Tse M, Molinoff P. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proc Natl Acad Sci U S A. 2004;101:10201-10204. ↗
  3. Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908. ↗
  4. Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol. 2019;134(5):909-917. ↗
  5. Thurston L, Hunjan T, Mills EG, Wall MB, Ertl N, Phylactou M, et al. Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder. J Clin Invest. 2022;132(19):e152341. ↗
  6. U.S. Food and Drug Administration / DailyMed. Bremelanotide Injection — US Prescribing Information. DailyMed (US FDA structured product label). 2019. NDA 210557. ↗
  7. Pfaus J, Giuliano F, Gelez H. Bremelanotide: An Overview of Preclinical CNS Effects on Female Sexual Function. J Sex Med. 2007;4(Suppl 4):269-279. ↗
  8. Shadiack AM, Sharma SD, Earle DC, Spana C, Hallam TJ. Melanocortins in the Treatment of Male and Female Sexual Dysfunction. Curr Top Med Chem. 2007;7(11):1137-1144. ↗
  9. Pfaus JG, Sadiq A, Spana C, Clayton AH. The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women. CNS Spectr. 2022;27(3):281-289. ↗
  10. Spana C, Jordan R, Fischkoff S. Effect of bremelanotide on body weight of obese women: Data from two phase 1 randomized controlled trials. Diabetes Obes Metab. 2022;24(6):1084-1093. ↗
  11. Semple EA, Harberson MT, Xu B, Rashleigh R, Cho J, et al. (Hill JW). Melanocortin 4 receptor signaling in Sim1 neurons permits sexual receptivity in female mice. Front Endocrinol (Lausanne). 2023;14:983670. ↗
  12. Borland JM, Kohut-Jackson AL, Peyla AC, Hall MA, Mermelstein PG, Meisel RL. Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder. Neuropharmacology. 2025;110299. ↗
  13. How A, Simon JA. Novel Pharmacologic Treatments of Female Sexual Dysfunction. Clin Obstet Gynecol. 2025. ↗
  14. Fuhrman J, et al. Practical considerations and emerging approaches for the management of vasomotor and sexual symptoms. Expert Rev Clin Pharmacol. 2025. ↗
  15. Rowen T, et al. Evaluation and management of hypoactive sexual desire disorder in women. Recommendations from a multidisciplinary panel. Sex Med Rev. 2026. ↗
  16. Dhillon S, Keam SJ. Bremelanotide: First Approval. Drugs. 2019;79:1599-1606. ↗
  17. White WB, Myers MG, Jordan R, Lucas J. Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide. J Hypertens. 2017;35(4):761-768. ↗
  18. Clayton AH, Lucas J, DeRogatis LR, Jordan R. Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants. Clin Ther. 2017;39(3):514-526.e14. ↗
  19. Clayton AH, Kingsberg SA, Portman D, Sadiq A, Jordan R, Lucas J, Spana C, Simon JA. Safety Profile of Bremelanotide Across the Clinical Development Program. J Womens Health (Larchmt). 2022;31(2):171-182. ↗
  20. National Institute of Diabetes and Digestive and Kidney Diseases (LiverTox). Bremelanotide - LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. NCBI Bookshelf (LiverTox). 2021. ↗
  21. Mestria S, Odoardi S, Frison G, Strano Rossi S. LC-HRMS characterization of the skin pigmentation and sexual enhancers melanotan II and bremelanotide sold on the black market of performance and image enhancing drugs. Drug testing and analysis. 2021. ↗
  22. Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clinical toxicology (Philadelphia, Pa.). 2012. ↗
  23. Bardhan M, Anand A, Javed A, Chilo MA, Khan N, Garg T. Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases. Diseases (Basel, Switzerland). 2025. ↗
  24. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006. ↗
  25. Hedlund P. PT-141 Palatin. Current opinion in investigational drugs (London, England : 2000). 2004. ↗
  26. Al Shaer D, Al Musaimi O, Albericio F, de la Torre BG. 2019 FDA TIDES (Peptides and Oligonucleotides) Harvest. Pharmaceuticals (Basel, Switzerland). 2020. ↗