Bremelanotide, developed as PT-141, is a synthetic cyclic peptide that activates melanocortin receptors. Its clinical evidence concerns distressing low sexual desire in a defined group of premenopausal women. Two large placebo-controlled trials found improvements in desire and related distress over 24 weeks, while the prespecified count of satisfying sexual events showed no significant treatment difference. Those results explain both the prescription product Vyleesi's role and the importance of asking which aspect of sexual experience a study measured.
Overview
Bremelanotide belongs to the α-melanocyte-stimulating hormone family of analogues. Its seven-residue structure contains a ring and a D-phenylalanine residue, features that influence how a peptide presents itself to receptors and survives enzymatic breakdown. Vyleesi supplies the acetate salt in a defined subcutaneous formulation. PT-141 is a development name for bremelanotide; studies of a different melanocortin or delivery system retain their own identity.
Molecular profile
- Form
- Bremelanotide acetate in Vyleesi; neutral parent composition listed separately Source
- Structure
- Cyclic heptapeptide melanocortin analogue containing D-phenylalanine Source
- Molecular formula
- C50H68N14O10 (free base); acetate: C50H68N14O10·xCH3COOH, 1 ≤ x ≤ 2 Source
- Molecular mass
- 1025.2 Da (free base) Source
- Development name
- PT-141 Source
Forms and derivatives
Bremelanotide acetate / Vyleesi
The acetate salt and defined subcutaneous prescription formulation supply the material behind the approved clinical program.
Historical intranasal bremelanotide
Earlier nasal formulations were studied during development. Their route-specific exposure and tolerability findings belong to those formulations.
The closest historical comparison is Melanotan II, whose original clinical pilot used a separate cyclic peptide with an amidated terminus. This chemical relationship helps explain their overlapping pigmentation and sexual-response research, while the clinical development programs pursued different outcomes. Dorr and colleagues (1996).
Uses and research areas
The current US indication is acquired, generalized hypoactive sexual desire disorder in premenopausal women: low desire causing marked distress or interpersonal difficulty, with causes such as a coexisting medical or psychiatric condition, relationship problems, or a medication or drug substance excluded. “Acquired” means the difficulty developed after an earlier period without it; “generalized” means it occurs across situations, partners and stimulation. Vyleesi's indication excludes men, postmenopausal women and sexual-performance enhancement. Vyleesi prescribing information.
Earlier research included women with sexual-arousal difficulties as well as desire disorder. That broader enrollment and the investigators' choice of outcome measures matter when comparing the phase 2 findings with the later registration trials. Desire, distress, erection, arousal and satisfaction describe related experiences, but each requires its own measurement. Clayton and colleagues (2016).
Mechanism of action
Melanocortin receptors translate peptide binding into cellular signals. Bremelanotide activates several subtypes; MC4 receptors in the nervous system contribute a plausible connection to sexual-response circuitry, and MC1 receptors in melanocytes account for pigmentation. The label identifies MC1 and MC4 activity as especially relevant at clinical exposures and leaves the precise pathway producing improved HSDD symptoms unresolved. A receptor map explains biological access to these systems without specifying how every individual's desire will change. Vyleesi prescribing information.
This central melanocortin approach grew from observations that related peptides could produce sexual responses alongside pigment effects. The modern trial program therefore evaluated subjective desire and distress directly, rather than relying on a physiological arousal response as a proxy for symptom relief. Kingsberg and colleagues (2019).
Pharmacokinetics
The current label reports a mean terminal plasma half-life of about 2.7 hours after subcutaneous Vyleesi, with a reported range of 1.9–4.0 hours. The FDA's BMT-107 review synopsis identifies healthy female and male participants and describes biphasic parent-peptide decline. It also distinguishes intact bremelanotide from total radioactive material, which includes breakdown products. FDA multidisciplinary review.
Population: Healthy female and male adults in BMT-107; denominator not extracted from acquired synopsis. Administration: Single subcutaneous administration in a monitored pharmacokinetic study. Analyte: Parent bremelanotide in plasma.
A simple terminal-elimination model uses the approximately 2.7-hour mean half-life reported in the FDA BMT-107 synopsis for healthy women and men after subcutaneous administration. The relative decline follows C/C0 = 2^(−t/2.7); it does not trace measured absorption, the earlier distribution phase or the duration of sexual effects.
U.S. Food and Drug Administration. NDA 210557: Vyleesi (bremelanotide), Multi-Discipline Review. 2019. Reference ID 4416675; Cosette Pharmaceuticals, Inc. VYLEESI (bremelanotide injection): Full prescribing information. DailyMed. Updated November 13, 2025; accessed October 13, 2026. FDA review printed p. 60, BMT-107 Human ADME synopsis; current label §12.3
Peptide-bond hydrolysis produces smaller molecules that can be cleared through urine and other routes. Plasma disappearance consequently answers a different question from how long a change in desire, nausea or blood pressure persists. The underlying exposure study and the clinical symptom trials measure those processes separately.
Research findings
The exploratory desire and arousal trial
Clayton and colleagues randomized 397 premenopausal women in a 12-week dose-finding study; 327 contributed efficacy data. A pooled comparison of two selected active groups found a mean increase of 0.7 satisfying sexual events per month versus 0.2 with placebo, alongside improvements in sexual-function and distress scores. The pooling and broader diagnostic population make this an exploratory result that preceded the more specific phase 3 program. Original phase 2 report.
Desire and distress in RECONNECT
The two RECONNECT trials assigned 1,267 premenopausal women with acquired, generalized HSDD to subcutaneous bremelanotide or placebo for 24 weeks. Investigators assessed reported desire, distress about low desire and the number of satisfying sexual events. Across the trials, the improvement beyond placebo averaged 0.35 points on the desire score and 0.33 points on the distress item; both comparisons met the studies' statistical thresholds. The number of satisfying events did not increase more than with placebo. A later exploratory analysis asked what proportion of encounters was satisfying, which is a different question from how many satisfying encounters occurred. Safety data were available for 1,247 women and the defined efficacy analysis included 1,202. More women withdrew from bremelanotide in both trials, so missing follow-up affects interpretation of the averages. Kingsberg and colleagues (2019).
Longer follow-up among selected participants
Of 856 eligible core-trial completers, 684 entered an additional 52-week open-label extension and 272 completed it. Continuing participants reported maintained symptom improvements, and the study supplied longer tolerability observations. Participants knew they were receiving active treatment, and the substantial loss from enrollment to completion restricts how well their experience represents everyone who starts therapy. The extension follows the original cohorts rather than adding another independent controlled trial. Simon and colleagues (2019).
Safety and tolerability
Nausea occurred in 40.0% of active-treatment participants versus 1.3% with placebo in RECONNECT. Flushing and headache were also more frequent. These burdens help explain why trial retention deserves attention alongside improved symptom scores. Kingsberg and colleagues (2019).
Vyleesi can transiently raise blood pressure and lower heart rate; uncontrolled hypertension and known cardiovascular disease are contraindications. Focal hyperpigmentation occurred in about 1% of phase 3 participants. A separate repeated-exposure study reported 38% after eight days, a substantially different exposure context. Pigment changes did not have confirmed resolution in every patient. Delayed gastric emptying can affect oral medicines, including naltrexone. Current prescribing information, safety sections.
What the research means
Bremelanotide has controlled evidence for improving two patient-reported dimensions of acquired, generalized HSDD in the population studied. The null satisfying-event count is useful because symptom relief and the frequency of satisfying encounters can diverge. Relationships, opportunities, preferences and treatment tolerability contribute to that broader experience, which one receptor-targeting intervention cannot summarize.
The open-label extension adds information about people who continued treatment, while the clinical indication and contraindications define a narrower application than the broad sexual-enhancement claims often attached to the PT-141 name. Its strongest evidence remains the specified formulation and trial population.
FAQs
What does PT-141 mean?
PT-141 is a development name for bremelanotide. The Vyleesi trial program used a defined subcutaneous formulation; the name alone does not identify the contents of a separate preparation.
Did RECONNECT increase the number of satisfying sexual events?
The prespecified event-count comparison was not statistically significant. Desire and distress scores improved on average, while the later proportion-of-encounters analysis addressed a different question. RECONNECT report.
How convincing is the year-long extension?
The extension followed women who had completed the original trials and knew they were receiving bremelanotide. Of 684 who entered, 272 completed the additional year. Their reports describe the experience of people who continued treatment, while the absence of a placebo group and the many departures make it difficult to predict how long benefits last for everyone who starts. Simon and colleagues.
Why do skin and cardiovascular effects appear on a sexual-desire page?
Melanocortin receptors act in several tissues. Pigmentation and cardiovascular observations are clinically relevant effects of the tested drug, so the benefit assessment includes those systems as well as sexual symptoms.
Comparisons and related reading
Melanotan II provides the historical cyclic-melanocortin comparison, afamelanotide shows a clinical program centered on skin pigmentation and light tolerance, and kisspeptin-54 illustrates a different receptor system being explored for sexual-brain processing. Comparing their actual populations and outcomes is more informative than grouping them under sexual or tanning peptides.
References
An exploratory trial found benefit on several patient-reported measures in a broader diagnostic population.
Symptom scores improved while the specified event-count endpoint did not.
Longer observations came from a selected group with substantial attrition.
Defines the approved population, acetate identity, subcutaneous pharmacokinetics and safety findings in their study contexts.
The original Melanotan II pilot identifies the separate amidated cyclic peptide from which the bremelanotide development line arose.
The BMT-107 synopsis identifies healthy female and male participants, intact-plasma kinetics and the distinction between parent peptide and total radiolabel.
Glossary
- HSDD
- Hypoactive sexual desire disorder: distressing low desire assessed within its medical, medication and relationship context.
- Melanocortin receptor
- A receptor family activated by melanocortin peptides; its subtypes have different tissue distributions and physiological roles.
- Modified intention-to-treat
- An efficacy analysis of a defined subset of randomized participants, according to the trial’s inclusion rules.
- Open-label extension
- Follow-up in which participants and investigators know the treatment being received.