PT-141, chemically known as bremelanotide, is a synthetic cyclic heptapeptide and an active metabolite of melanotan II. Originally developed as a tanning peptide, research pivoted toward its central nervous system effects after subjects reported unexpected arousal responses. Unlike PDE5 inhibitors such as sildenafil — which act peripherally on vascular tissue — PT-141 operates through the central melanocortin system, making it mechanistically distinct. It received FDA approval in 2019 as Vyleesi for hypoactive sexual desire disorder (HSDD) in premenopausal women.
PT-141 is a cyclic heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. The cyclization via a lactam bridge between Asp and Lys residues provides enhanced metabolic stability versus linear analogs.
Molecular formula: C50H68N14O10. Molecular weight: 1,025.2 g/mol. CAS number: 189691-06-3. Classification: cyclic melanocortin receptor agonist.
The D-phenylalanine substitution at position 4 is critical for receptor binding stability. The N-acetyl norleucine at the N-terminus replaces the methionine of native α-MSH, eliminating oxidative susceptibility without meaningful loss of receptor affinity.
PT-141 is a non-selective agonist of the melanocortin receptor family, with affinity ranked MC1R > MC4R > MC3R > MC5R > MC2R. At pharmacologically relevant doses, MC4R binding in the medial preoptic area (mPOA) of the hypothalamus is the primary driver of its studied CNS effects.
MC4R activation in the mPOA triggers downstream dopamine release in mesolimbic reward circuits. This is mechanistically different from erectile dysfunction drugs — PT-141 doesn't increase genital blood flow directly; it modulates the central desire and arousal signal. Researchers characterize this as targeting the motivation arm of sexual response rather than the execution arm.
RECONNECT Trials (Phase 3, FDA Approval Basis): The Phase 3 RECONNECT program enrolled over 1,200 premenopausal women with HSDD. Participants receiving 1.75 mg subcutaneous injection as-needed showed statistically significant improvements in FSFI desire domain scores and reductions in FSDS-DAO distress scores versus placebo over 24 weeks. More than 3,500 patients were exposed across all development trials with no immunogenicity signals detected.
Male Sexual Function Research: Earlier Phase 2 data explored PT-141 in males with erectile dysfunction. Intranasal formulations above 7 mg produced statistically significant erectile responses versus placebo in healthy volunteers and men with mild-to-moderate ED.
PT-141 is studied in: pharmacology of the melanocortin system, CNS regulation of sexual function, hypoactive sexual desire disorders, hypothalamic peptide signaling, and comparative studies against PDE5 inhibitor mechanisms. Its FDA-approved status provides one of the more robust published clinical safety datasets for any research peptide.
Form: lyophilized powder. Purity: ≥98% HPLC verified. Storage: −20°C, protected from light and moisture. Reconstitution reference: bacteriostatic water recommended in the published research literature.
For research use only. Not for human consumption.
PT-141 binds all five melanocortin receptor subtypes (MC1R through MC5R), with highest affinity for MC1R and functionally significant activity at MC4R in the hypothalamus.
Sildenafil inhibits PDE5 to increase local blood flow — a peripheral vascular mechanism. PT-141 acts centrally via MC4R to increase dopamine release in reward circuits, modulating desire rather than vascular response.
Yes — as Vyleesi (1.75 mg SC) for HSDD in premenopausal women, approved June 2019.
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