PT-141 (Bremelanotide)

FDA-approved (Vyleesi®) melanocortin agonist for female hypoactive sexual desire disorder. Works through central MC4R pathway to increase sexual desire, not just arousal.

Overview

Also Known As

Bremelanotide, Vyleesi, BMT-141, Palatin Technologies PT-141

Mechanism of Action

MC4R agonist in hypothalamus modulating dopaminergic and oxytocinergic pathways involved in sexual desire. Central neurological mechanism affecting desire (not vascular/mechanical). Also activates MC1R (mild tanning) and MC3R.

Product

Bremelanotide, Vyleesi, BMT-141, Palatin Technologies PT-141 vial

Dosing & Administration

Typical protocols and routes

Half-Life

Approximately 2.7 hours

Administration Routes

subcutaneous

Dosing Protocols

Provider protocol: 2 mg subcutaneous injection, 1-2 hours before anticipated sexual activity. Reconstitute 10 mg vial with 1 mL bacteriostatic water, draw 20 units per dose (5 doses per vial). Maximum one dose per 24 hours. FDA-approved Vyleesi uses a 1.75 mg auto-injector dose.

Research

Key findings and status

Key Research Findings

RECONNECT Phase III (2 trials, 1200+ women): significant improvement in sexual desire and reduced distress in HSDD. Kingsberg et al. (2019, Ob/Gyn): pivotal results. Phase II trials showed efficacy for male ED. FDA-approved 2019 as first on-demand HSDD treatment.

Detailed Information

PT-141, marketed as Vyleesi® (bremelanotide), is a synthetic cyclic heptapeptide melanocortin receptor agonist and the first FDA-approved on-demand treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women. It was derived from Melanotan II and specifically developed to target sexual dysfunction through central melanocortin pathways.

Mechanism of Action

Bremelanotide acts primarily on MC4R (melanocortin-4 receptor) in the central nervous system, particularly in hypothalamic areas involved in sexual desire, arousal, and reward. Unlike phosphodiesterase-5 inhibitors (e.g., sildenafil) which act on vascular smooth muscle, bremelanotide works through a central neurological mechanism, directly influencing sexual desire rather than just the mechanical aspects of sexual function.

MC4R activation in the hypothalamus modulates dopaminergic and oxytocinergic pathways involved in sexual motivation and arousal. This mechanism makes it effective for desire-based sexual dysfunction — a category of conditions that was previously untreatable with existing pharmacotherapy.

Clinical Evidence

FDA approval was based on the RECONNECT Phase III program, consisting of two randomized, double-blind, placebo-controlled trials enrolling over 1,200 premenopausal women with HSDD. Treatment with bremelanotide 1.75 mg subcutaneous (self-administered at least 45 minutes before anticipated sexual activity) resulted in statistically significant increases in sexual desire (measured by FSDS-DAO desire domain score) and reductions in distress related to low sexual desire compared to placebo.

Kingsberg et al. (2019, Obstetrics & Gynecology) reported the pivotal trial results: 35% of bremelanotide-treated patients experienced clinically meaningful improvement in desire versus 31% with placebo. While the absolute difference was modest, the mechanism represents a novel approach to a condition with no prior approved treatments.

Male sexual dysfunction studies showed efficacy for erectile dysfunction in Phase II trials, though development focused on the female HSDD indication.

Safety & Legal

Side Effects & Warnings

Nausea (40%, most common), flushing, headache, injection site reactions. Transient blood pressure increase (contraindicated in uncontrolled hypertension). Hyperpigmentation with repeated use (darkening of skin, gums, breasts). Not for use with naltrexone.

Legal Status

FDA-approved as Vyleesi (2019) for HSDD in premenopausal women. Prescription required.

Molecular Data

Chemical properties

Molecular Weight

1025.18 g/mol

Amino Acid Sequence

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH (differs from MT-II by C-terminal hydroxyl instead of amide)