PT-141 (Bremelanotide)
PT-141 (bremelanotide / Vyleesi) — evidence, the discovery story & status

Class: peptide
Synonyms: PT-141
bremelanotide
brand Vyleesi
a melanocortin (MC4R) agonist
the active derivative of Melanotan II (#32). Developer: Palatin Technologies. INCI: none
Function tags: sexual desire / arousal (approved: female HSDD)
erectile function (off-label)
Overall evidence grade: B
WADA prohibited: no
WADA note: Sport: PT-141/bremelanotide is not currently on the WADA Prohibited List (the melanocortin class could see future scrutiny).
Last updated: 2026-07-11

In brief: PT-141 (bremelanotide) is a central-acting melanocortin MC4R agonist and the active derivative of the tanning peptide Melanotan II. It is FDA-approved as Vyleesi for HSDD in premenopausal women — one of the very few consumer-sexual-health peptides with real FDA approval — but the effect is modest, the approval does not cover the popular men's-ED use (that program was abandoned on blood-pressure grounds), and it carries real risks (blood pressure, hyperpigmentation) that hype content omits.

## Identity a synthetic **cyclic heptapeptide** (7 amino acids, cyclically constrained for stability), a melanocortin-receptor agonist — strongest at **MC4R**, with some MC1R/MC3R activity. It is a metabolite/derivative of Melanotan II, engineered to be **more MC4R-selective (sexual effect) and less MC1R (tanning)**. ## Development & history - In the **1980s at the University of Arizona**, **Mac E. Hadley** and **Victor J. Hruby** were developing α-MSH analogs as **sunless-tanning agents** (to induce protective melanin without UV), synthesising Melanotan-I and **Melanotan II**.
- **The discovery:** while self-experimenting with Melanotan II, one of the scientists **accidentally injected roughly twice the intended dose and experienced an ~eight-hour erection, along with nausea and vomiting.** That unexpected central effect (later documented in a 1996 pilot trial and a 1998 placebo-controlled crossover study, Wessells et al., J Urology — erections in 8 of 10 men) redirected an entire research line from tanning toward **sexual function**. Hadley published it as *"Discovery that a melanocortin regulates sexual functions in male and female humans"* (Peptides, 2005).
- **Palatin Technologies** developed **bremelanotide (PT-141)** from Melanotan II for sexual dysfunction. An **intranasal** formulation was trialed for **erectile dysfunction** (Phase 2b; 2007 BJU Int: ~60% of men with mild-moderate ED responded vs 27% placebo) — but the **ED program was abandoned because of blood-pressure increases** (and PDE5-inhibitor competition).
- Palatin **pivoted to a subcutaneous** formulation for **HSDD in premenopausal women** (no approved drug existed then bar flibanserin). Two Phase 3 **RECONNECT** trials led to **FDA approval of Vyleesi in June 2019** — one of only two FDA-approved drugs for female sexual dysfunction. ## Mechanism (as proposed) a **central** melanocortin agonist — activates **MC4R** (and MC3R) in the hypothalamus (paraventricular nucleus, medial preoptic area), driving sexual **desire and arousal** through dopaminergic and oxytocin pathways and autonomic output to the pelvis. This is fundamentally different from PDE5 inhibitors (sildenafil), which act **peripherally on blood flow** — PT-141 is better described as a **desire** enhancer than a blood-flow one, and its effect does not depend on hormone levels or direct stimulation.

Evidence grades by outcome:
outcome: HSDD in premenopausal women (approved)
grade: B
base: Phase 3 RECONNECT; FDA-approved 2019
effect: Modest but significant ↑ desire / ↓ distress (FSFI effect ~0.49–0.61; NNT ~12)
caveat: Approved + RCT-backed, but the effect is modest
outcome: Erectile dysfunction (men, off-label)
grade: C
base: Phase 2 (2007 intranasal, 60% vs 27%); precursor crossover data
effect: Promising erectogenic effect
caveat: No completed Phase 3; the ED program was abandoned on blood-pressure grounds; not approved
outcome: General libido / arousal (both sexes, gray market)
grade: D
base: Extrapolated
effect: Suggestive
caveat: Not studied or approved for this
outcome: Safety
base: Approved-drug label + trials
effect: Characterised
caveat: Nausea (~40% first dose), flushing, headache, transient BP increase (the reason ED development stopped), focal hyperpigmentation with repeated use; caution in hypertension / CVD

Legal status:
region: US
status: Approved / prescription
note: FDA-approved as Vyleesi (June 2019) for acquired, generalized HSDD in premenopausal women (subcutaneous, as-needed). Men's ED / general libido use is off-label — not approved. Compounded PT-141 is widely dispensed via 503A/503B wellness channels at variable quality.
region: EU
status: availability and approval status vary (confirm before relyin
note: availability and approval status vary (confirm before relying on it).

Cosmetic claims:

Note: Reference entry — not sold here. PT-141 is FDA-approved (as Vyleesi) — but only for a narrow indication in women; the popular men's-ED use is off-label and was abandoned in development on safety grounds. A prescription/compounded drug, not a wellness supplement. No dosing published here.

Sources:
Hadley ME. Discovery that a melanocortin regulates sexual functions in male and female humans. Peptides. 2005.
Wessells H, et al. (Melanotan-II / bremelanotide erectile-response crossover trials.) J Urol, 1998; BJU Int, 2007 (intranasal Phase 2).
Kingsberg SA, et al. (RECONNECT Phase 3 trials of bremelanotide for HSDD.) 2019.
FDA prescribing information — Vyleesi (bremelanotide), Palatin/AMAG.