Educational Reference · Research-Use-Only
PT-141 (Bremelanotide): Mechanism, Research, and Regulatory Status
A research-grade overview of PT-141 (Bremelanotide) — what it is, how it works at the molecular level, what published studies have shown, and answers to the questions researchers ask most.
Last reviewed 2026-07-28
What is PT-141 (Bremelanotide)?
Bremelanotide is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone and acts as a non-selective melanocortin receptor agonist. FDA-approved labeling states that it activates several melanocortin receptor subtypes with a rank order of potency of MC1R, MC4R, MC3R, MC5R and MC2R, and that binding at MC1R and MC4R is the most relevant at therapeutic exposures. Melanocortin receptors are class A G-protein-coupled receptors signaling predominantly through Gs and adenylyl cyclase, raising intracellular cAMP and activating protein kinase A.
MC4R is expressed widely in the central nervous system, including hypothalamic nuclei implicated in appetite, autonomic outflow and sexual behavior, which is the basis for the receptor's investigation in this context. Structural modifications relative to native alpha-MSH — the D-phenylalanine substitution and the lactam-bridged macrocycle — confer resistance to enzymatic degradation and a conformational constraint that improves receptor affinity relative to the linear parent peptide. Notably, the approved labeling states explicitly that the mechanism by which bremelanotide produces its clinical effect is unknown, so receptor pharmacology should not be over-interpreted as a settled explanation of the clinical endpoint.
Off-target MC1R agonism is the pharmacological basis for the cutaneous flushing and hyperpigmentation effects documented in the trial program.
Research highlights
What published peer-reviewed research and preclinical studies have established about PT-141 (Bremelanotide):
- 01Bremelanotide is a non-selective melanocortin receptor agonist with a labeled potency order of MC1R > MC4R > MC3R > MC5R > MC2R.
- 02It is a cyclic heptapeptide analog of alpha-MSH, derived from the melanocortin agonist program described by Molinoff and colleagues (2003).
- 03In two 24-week randomized Phase 3 trials, both co-primary endpoints reached statistical significance versus placebo (Kingsberg 2019).
- 04The most frequent drug-related adverse events in the open-label extension were nausea (40.4%), flushing (20.6%) and headache (12.0%) (Simon 2019).
- 05Pooled safety data across the development program were published separately (Clayton 2022).
- 06Research-grade bremelanotide powder is not the approved finished drug product and is not manufactured to pharmaceutical GMP standards.
Published clinical and preclinical research
RECONNECT Study 301 and Study 302 (pooled report)
Phase 3 · 2019FSFI-D improved by 0.30 (Study 301, P<.001) and 0.42 (Study 302, P<.001); FSDS-DAO item 13 changed by -0.37 (Study 301, P<.001) and -0.29 (Study 302, P=.005). Nausea, flushing and headache each occurred in at least 10% of treated patients.
RECONNECT open-label extension
Phase 3 (open-label extension) · 2019No new safety signals observed. Most frequent drug-related adverse events were nausea 40.4%, flushing 20.6% and headache 12.0%.
Frequently asked questions about PT-141 (Bremelanotide)
What is PT-141 (bremelanotide)?+
Bremelanotide is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone that acts as a non-selective melanocortin receptor agonist. Its structure includes a D-phenylalanine substitution and a lactam bridge between aspartate and lysine, giving a constrained macrocycle that resists enzymatic degradation.
Is research-grade PT-141 the same as the approved drug?+
No. The FDA approved VYLEESI (bremelanotide injection) in June 2019 as a finished, prescription pharmaceutical dosage form manufactured to GMP standards for a specific indication and population. Research-grade bremelanotide powder is not that product, is not GMP pharmaceutical material, and is supplied for laboratory research use only.
Why does melanocortin receptor selectivity matter?+
Bremelanotide is non-selective across melanocortin receptor subtypes. MC4R activity in the central nervous system is the subtype most associated with the studied endpoint, while MC1R agonism accounts for the cutaneous effects — flushing and focal hyperpigmentation — documented in the clinical program. Selectivity therefore determines which effects are on-target versus off-target in a given model.
How does it differ from Melanotan II?+
Both are melanocortin agonists derived from alpha-MSH, but they are distinct compounds with different structures and regulatory status. Bremelanotide has an approved finished drug product for one specific indication; Melanotan II has no approval in any jurisdiction and has been the subject of regulatory warnings in multiple countries. They should not be treated as interchangeable.
How should it be stored and reconstituted?+
Store lyophilized material at -20C, desiccated and protected from light. As a cyclic peptide it is more resistant to protease degradation than a comparable linear analog, but standard handling still applies: reconstitute with sterile or bacteriostatic water using gentle swirling, aliquot working stocks, and store reconstituted solutions at 2-8C for short-term laboratory use.
References & sources
Every citation below was resolved against its primary source before publication — each PMID against the PubMed record and each DOI through doi.org. Follow any link to read the paper at the publisher rather than taking our summary on trust.
- [1]Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstetrics and Gynecology. 2019. PMID: 31599840 DOI: 10.1097/AOG.0000000000003500
- [2]Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH. Long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder. Obstetrics and Gynecology. 2019. PMID: 31599847 DOI: 10.1097/AOG.0000000000003514
- [3]Clayton AH, Simon JA, Kingsberg SA, et al.. Bremelanotide for female sexual dysfunctions: a pooled analysis of safety. Journal of Women's Health. 2022. PMID: 35147466 DOI: 10.1089/jwh.2021.0191
- [4]Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences. 2003. PMID: 12851303 DOI: 10.1111/j.1749-6632.2003.tb03167.x
Where this data comes from
- —Citations & trial data: PubMed (NCBI, U.S. National Library of Medicine), Crossref and ClinicalTrials.gov.
- —Chemical identity: PubChem and UniProt. Where sources conflicted, the disputed value is omitted rather than guessed.
- —Regulatory status: U.S. FDA publications and, where applicable, the WADA Prohibited List. Compounding status changes frequently — verify against FDA directly before relying on it.
- —Purity, form and storage are handling and supplier conventions, not literature-derived values. Confirm against the lot-specific certificate of analysis.
Content last reviewed 2026-07-28. Compiled by Veridian Research from the primary literature. This page is an educational reference for laboratory researchers — it is not medical advice, and it describes no human use.
Regulatory status
Bremelanotide has an approved finished drug product: the FDA approved VYLEESI (bremelanotide injection) on 21 June 2019 under NDA 210557 for a specific indication in a specific population, supplied by prescription as a subcutaneous autoinjector. That approval is limited to that indication and does not extend to research-grade material. Research-grade bremelanotide powder is not the approved drug product, is not manufactured to pharmaceutical GMP standards, and is supplied for in vitro and laboratory research use only — not for human or veterinary use. An earlier intranasal formulation developed for a different indication did not reach approval.
Research-Use-Only Material
Specifications and certificate of analysis
PT-141 (Bremelanotide) is stocked as a research reagent. Analytical documentation — identity, purity and the lot-specific certificate of analysis — is published on the product record.
View specifications & COA →