PT-141 (Bremelanotide)

Pharmaceutical history and what the literature shows

• · Derived from Melanotan II research at the University of Arizona in the 1990s. Melanotan II was found to produce significant melanocyte-stimulating and central-nervous-system effects in rodent models.
• · PT-141 was synthesised as a cyclic, more metabolically stable analog of Melanotan II, with reduced UV-tanning activity but retained central effects in animal models.
• · Rodent studies demonstrated activation of MC4R in hypothalamic circuits in animal models. These findings informed the human clinical development programme.
• · Phase II and Phase III clinical trials in the US (Palatin Technologies) led to the 2019 FDA approval of subcutaneous Vyleesi for hypoactive sexual desire disorder in premenopausal women. This is the only approved indication globally.
• · The FDA label carries a boxed warning regarding transient blood pressure elevation and a contraindication with naltrexone-containing products. These pharmacological properties are present in the molecule regardless of formulation or jurisdiction.
• · No equivalent EU or UK regulatory submission has resulted in an MHRA marketing authorisation as of the date of this entry.

Adjacent compounds in the melanocortin-agonist class include Melanotan I and Melanotan II. PT-141 differs from both in receptor-subtype selectivity profile and in the absence of significant UV-tanning activity at lower concentrations.