PT-141 (Bremelanotide)

Melanocortin Receptor AgonistFDA-approved

Also known as: Bremelanotide, Vyleesi, PT141

An FDA-approved melanocortin receptor agonist that treats hypoactive sexual desire disorder (HSDD) in premenopausal women by acting directly on the central nervous system to increase sexual desire and arousal.

Overview

PT-141 (Bremelanotide) is a synthetic cyclic heptapeptide melanocortin receptor agonist, originally derived from the tanning peptide Melanotan II. During Melanotan II trials, researchers noticed significant pro-sexual side effects, leading to the development of PT-141 as a targeted sexual dysfunction treatment. Unlike PDE5 inhibitors (Viagra, Cialis) which work on the vascular system to facilitate erections, PT-141 works centrally in the brain by activating melanocortin-4 receptors (MC4R) in the hypothalamus, directly increasing sexual desire and arousal. It was FDA-approved in 2019 as Vyleesi for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women, making it the first ever on-demand injectable medication for female sexual dysfunction. Off-label, it is widely used by both men and women for enhanced libido and sexual function.

Mechanism of Action

PT-141 works through: (1) Agonism of melanocortin-4 receptors (MC4R) in the hypothalamus and limbic system, areas involved in sexual arousal and desire; (2) Also activates MC3R and MC1R to a lesser degree; (3) Increases dopaminergic signaling in brain regions associated with sexual motivation; (4) Unlike PDE5 inhibitors, it does not directly affect blood flow or vascular smooth muscle โ€” the effect is purely central/neurological; (5) Increases both spontaneous and solicited sexual desire; (6) Effects on MC1R can cause mild melanogenesis (skin darkening) at higher doses; (7) MC4R activation in the brainstem can trigger transient nausea.

Molecular Formula

C50H68N14O10

Molecular Weight

1025.18 g/mol

Sequence

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH

Dosage Protocols

Dose Range

1.75mg โ€“ 1.75mg

Frequency

As needed, at least 45 minutes before sexual activity

Route

subcutaneous

Cycle Length

As needed (max once per 24 hours, max 8 doses/month)

FDA-approved dose. Inject in the abdomen or thigh. Onset of effect typically 45-60 minutes. Do not exceed 8 doses per month per FDA labeling.

Source: FDA prescribing information (Vyleesi)

Side Effects

EffectSeverity
Nauseamoderate
Flushingmild
Headachemild
Injection site reactionsmild
Skin darkening (hyperpigmentation)mild
Elevated blood pressuremoderate

Pros & Cons

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FDA-approved with clinical trial data โ€” the first centrally-acting drug approved for female sexual desire

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Works on desire and arousal centrally โ€” addresses a different pathway than Viagra/Cialis

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Effective in both men and women for libido enhancement

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On-demand dosing โ€” use only when needed rather than daily

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Can work when PDE5 inhibitors have failed or are contraindicated

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High rate of nausea (~40%) which can be counterproductive to sexual activity

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Requires subcutaneous injection โ€” less convenient than oral medications

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Limited to 8 doses per month per FDA labeling due to skin darkening risk

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Transient blood pressure elevation โ€” caution in cardiovascular patients

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Expensive without insurance, and insurance coverage is limited

Research Studies

Legal Status

FDA-approved as Vyleesi (2019) for HSDD in premenopausal women. Prescription required. Also available through compounding pharmacies. Off-label use for male sexual dysfunction is common.

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