PT-141 — Research, Dosing & Price Guide

PT-141 (bremelanotide) is a synthetic melanocortin peptide and the only FDA-approved on-demand treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, marketed as Vyleesi. Originally derived from Melanotan-2 during clinical development, PT-141 was the first centrally-acting sexual dysfunction drug — it works in the brain rather than on peripheral blood flow, making it effective for desire-based dysfunction rather than purely mechanical arousal problems. It activates melanocortin-4 receptors (MC4R) in the hypothalamus to increase sexual desire and arousal in both men and women.

PT-141 is a cyclic heptapeptide (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-OH) structurally derived from Melanotan-2 but modified to eliminate melanogenesis while preserving MC4R-mediated sexual effects. Its mechanism of action is centrally mediated and fundamentally different from PDE5 inhibitors (Viagra, Cialis) or hormonal approaches. PT-141 selectively activates MC4R in the medial preoptic area (MPOA) and paraventricular nucleus (PVN) of the hypothalamus — brain regions that serve as integration centers for sexual motivation, arousal, and autonomic genital response. MC4R activation in the PVN triggers descending oxytocin and dopaminergic pathways that increase sexual desire at the motivational level while simultaneously activating autonomic pathways to the sacral spinal cord that mediate genital arousal responses. In males, this descending pathway activates parasympathetic neurons in the sacral erection center (S2–S4), producing penile erection through a mechanism entirely independent of the NO/cGMP/PDE5 cascade targeted by sildenafil. This means PT-141 can produce erections in men who do not respond to PDE5 inhibitors, particularly those with psychogenic erectile dysfunction or mixed-etiology ED where desire is a significant component. In females, MC4R activation increases genital blood flow, vaginal lubrication, and subjective sexual desire through the same hypothalamic pathways. The distinction is critical: PT-141 increases wanting (desire/motivation) rather than merely enabling physical arousal — it addresses the psychological and neurological roots of sexual dysfunction. PT-141 also modulates dopamine release in the mesolimbic reward pathway, contributing to increased anticipatory pleasure and sexual motivation. Unlike Melanotan-2, PT-141 has minimal MC1R activity (no significant tanning) and negligible MC3R and MC5R effects, making its pharmacological profile much cleaner for sexual indication use. The peptide has a half-life of approximately 2.7 hours after subcutaneous injection, with peak sexual effects occurring 1–3 hours post-dose and duration of action lasting approximately 6–12 hours. Effects on desire may persist up to 24 hours in some individuals.

• The RECONNECT Phase III trials (n=1,247 premenopausal women) demonstrated bremelanotide significantly increased sexual desire and reduced distress associated with low sexual desire compared to placebo, leading to FDA approval in 2019
• Diamond et al. (2006) in the International Journal of Impotence Research showed PT-141 induced erections in 8 of 10 men with erectile dysfunction, including those who had failed sildenafil treatment — demonstrating its unique mechanism of action
• Safarinejad (2008) in the Journal of Sexual Medicine confirmed PT-141 improved erectile function, sexual desire, and intercourse satisfaction in men with ED in a randomized placebo-controlled trial
• Pfaus et al. (2004) published foundational research in PNAS showing bremelanotide enhanced solicitation behaviors and lordosis in female rats through MC4R activation in the hypothalamus
• Clayton et al. (2016) in Obstetrics & Gynecology showed clinically meaningful increases in desire and decreases in distress in the pivotal trials leading to FDA submission
• Wessells et al. (2003) demonstrated that PT-141's erectogenic effect was mediated centrally via the nervous system, not peripherally — a mechanistic breakthrough distinguishing it from all prior ED treatments
• A 2007 study in the Journal of Urology showed PT-141 nasal spray improved erectile function in a dose-dependent manner, though the intranasal formulation was later abandoned due to blood pressure concerns
• Research in Pharmacology, Biochemistry and Behavior (2006) demonstrated PT-141's MC4R selectivity and absence of significant melanogenic activity, distinguishing it pharmacologically from Melanotan-2

• FDA-approved dose (Vyleesi): 1.75 mg subcutaneous injection in the abdomen or thigh, at least 45 minutes before anticipated sexual activity
• Maximum frequency: once per 24 hours; no more than 8 doses per month per FDA labeling
• Off-label male dosing: 1.0–2.0 mg subcutaneous injection 1–3 hours before sexual activity
• Some male protocols use lower doses of 0.5–1.0 mg to reduce side effects while maintaining efficacy
• Start with the lowest effective dose — many users find 1.0 mg sufficient, and side effects are dose-dependent
• Do not pre-treat with antiemetics containing dopamine antagonists, as they may reduce PT-141's pro-sexual effects
• For nausea management: start with 0.5 mg to assess tolerance; nausea typically diminishes with subsequent doses
• Not intended for daily use — on-demand dosing preserves efficacy and minimizes side effects
• Effects onset: 45 minutes to 2 hours; peak effects at 1–3 hours post-injection
• Avoid concurrent use with PDE5 inhibitors unless under medical supervision (theoretical risk of additive blood pressure effects)

Known Side Effects

• Nausea — the most common side effect, occurring in approximately 40% of users in clinical trials; usually mild-moderate and peaks 1–2 hours post-injection; diminishes significantly with repeated use
• Facial flushing — warmth and redness lasting 30–90 minutes, reported in approximately 20% of users
• Injection site reactions — pain, redness, or bruising at the subcutaneous injection site
• Headache — reported in approximately 10% of clinical trial participants
• Transient blood pressure elevation — the intranasal formulation was abandoned due to this concern; the subcutaneous route has a more favorable hemodynamic profile, but blood pressure should be monitored in hypertensive individuals
• Skin hyperpigmentation — rare at PT-141 doses due to low MC1R activity, but darkening of facial skin or gums has been reported with repeated use; the FDA label recommends limiting to 8 doses per month partly for this reason
• Fatigue or drowsiness — reported by some users after the sexual effects subside
• Priapism — theoretically possible given the erectogenic mechanism, though no cases were reported in clinical trials at approved doses

Safety Profile

PT-141 (bremelanotide) has a well-characterized safety profile from extensive Phase I–III clinical trials and post-marketing surveillance following its 2019 FDA approval. The RECONNECT trials enrolled over 1,200 women with a favorable safety profile. The most significant safety consideration is transient blood pressure elevation — the earlier intranasal formulation was associated with clinically significant BP increases, leading to reformulation as a subcutaneous injection with a better hemodynamic profile. Nevertheless, PT-141 is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease. The FDA labeling limits use to 8 doses per month to minimize the risk of hyperpigmentation with repeated MC1R exposure. There is no evidence of physical dependence, tolerance, or withdrawal. Drug interactions include caution with naltrexone (reduced PT-141 efficacy via opioid pathway crosstalk) and PDE5 inhibitors (potential additive hypotension). Hepatic impairment does not require dose adjustment. Renal impairment data is limited; caution advised in severe renal disease.

45 minutes–2 hours post-injection: Nausea and flushing are most common in this window, particularly with the first 1–3 uses. Nausea is usually mild and passes within 1–2 hours. Alongside the side effects, a growing sense of sexual desire and awareness begins. 2–4 hours: Peak sexual effects. Users describe a distinctly increased desire for intimacy — not a forced arousal but a natural amplification of sexual interest and responsiveness. Physical arousal responses are heightened: men report firmer erections with less mental effort, women report increased genital sensation, lubrication, and desire. Unlike PDE5 inhibitors, the effect feels motivational rather than mechanical. 4–12 hours: Sexual enhancement gradually diminishes but remains noticeable. Some users report a lingering 'afterglow' of increased desire and sensitivity for up to 24 hours. Subsequent uses: Nausea typically decreases significantly after the first 2–3 doses while sexual effects remain consistent. Most users find their optimal dose within 2–3 uses. Long-term: No tolerance development has been observed with on-demand use (limited to 8 times per month). Effects remain consistent over months of intermittent use.

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