PT-141 (Bremelanotide): A Melanocortin Receptor Agonist

PT-141 is the research designation for bremelanotide, a synthetic cyclic peptide that acts as an agonist at melanocortin receptors. It is studied as a stabilized analog of α-melanocyte-stimulating hormone (α-MSH). This article summarizes published, peer-reviewed research on the bremelanotide compound as external scientific literature. It makes no therapeutic claims about any product, and it is not medical guidance. The research-grade compound is intended for laboratory research use only.

Mechanism: A Central, Not Vascular, Target

What made bremelanotide scientifically distinctive is where it acts. Molinoff and colleagues described PT-141 as a melanocortin agonist and situated its activity in the central melanocortin system rather than the peripheral vasculature (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).

Bremelanotide is a non-selective agonist across melanocortin receptor subtypes, with activity at MC3R and MC4R that are expressed in the central nervous system. This is a mechanistically different approach from vasoactive compounds that act on peripheral blood flow — the melanocortin pathway operates upstream, in neural signaling, rather than on vascular smooth muscle.

Why the mechanism matters: because bremelanotide engages central melanocortin receptors rather than a vascular target, its research literature sits within melanocortin-system neuroscience — a distinct body of work from the vascular pharmacology of other compounds studied in the same general area.

From α-MSH to a Stabilized Cyclic Peptide

Native α-MSH is a linear peptide that is rapidly degraded, which limits its usefulness as a research tool. Bremelanotide is an engineered cyclic analog designed for greater metabolic stability. Its structure is a cyclic heptapeptide with two defining features:

  • A side-chain-to-side-chain lactam bridge that closes the peptide into a ring (a 2→7 lactam between the aspartate and lysine side chains), constraining its conformation
  • An N-terminal acetyl-norleucine (Ac-Nle) cap in place of the methionine found in native α-MSH, removing an oxidation-prone residue and blocking the N-terminus

The full standard representation is Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH. The inclusion of a D-phenylalanine and the ring closure are characteristic medicinal-chemistry strategies for making a peptide more resistant to enzymatic breakdown while preserving receptor activity.

Published Clinical Research on Bremelanotide

Bremelanotide has an unusually well-documented clinical research record for a compound in this space. The following are published, peer-reviewed studies of the bremelanotide compound, summarized here as external literature.

Early work evaluated an intranasal formulation. Diamond and colleagues reported a double-blind, placebo-controlled evaluation of intranasal PT-141 in healthy males and men with erectile dysfunction (Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB. Int J Impot Res. 2004;16(1):51-59). This early research route was later set aside; blood-pressure effects observed with intranasal delivery are frequently cited as a reason the program moved to subcutaneous administration.

Subsequent research shifted to subcutaneous dosing and to female hypoactive sexual desire disorder (HSDD) as the studied endpoint. A randomized, placebo-controlled dose-finding trial in premenopausal women was published by Clayton and colleagues (Clayton AH, Althof SE, Kingsberg S, et al. Womens Health (Lond). 2016;12(3):325-337), followed by two identically designed randomized phase 3 trials (the RECONNECT studies) reported by Kingsberg and colleagues (Kingsberg SA, Clayton AH, Portman D, et al. "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials." Obstet Gynecol. 2019;134(5):899-908).

The phase 3 research described above supported an approved pharmaceutical form of bremelanotide for a specific medical indication. That approved medicine is a distinct, regulated product. The research-grade compound described on this page is not that medicine, is not for human use, and is supplied for laboratory research only. The studies above are cited as external scientific literature about the bremelanotide compound, not as claims about this product.

Molecular Reference & Research Status

PropertyValue
Research nameBremelanotide
SequenceAc-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH
ClassCyclic heptapeptide; melanocortin receptor agonist
Molecular formulaC₅₀H₆₈N₁₄O₁₀ (free peptide)
Molecular weight1,025.18 Da (free peptide)
CAS number189691-06-3

Note on form: molecular values above are for the free peptide. Research-grade material is sometimes supplied as an acetate salt, which carries a different formula and mass; a Certificate of Analysis identifies the exact form of a given batch. This compound is for in vitro and preclinical laboratory research only. Nothing here is medical, diagnostic, or therapeutic advice.