PT-141 [Peptide]

Description

What is PT-141 (Bremelanotide)?

PT-141, also known by its INN Bremelanotide, is a synthetic cyclic heptapeptide melanocortin receptor agonist derived from Melanotan II – itself a synthetic cyclic analogue of alpha-melanocyte-stimulating hormone (α-MSH). PT-141’s sequence is based on the core pharmacophore of Melanotan II with the removal of the C-terminal amide and addition of a carboxylic acid at the C-terminus, producing a compound that retains high-affinity melanocortin receptor agonism – particularly at MC4R – without the skin-tanning (melanogenic) activity associated with MC1R agonism that characterised Melanotan II.

The compound was first described in the literature in 2003 under the investigational code PT-141. It was developed from Melanotan II through modifications aimed at eliminating pigmentation activity while preserving CNS-mediated sexual arousal effects. Bremelanotide (marketed as Vyleesi) received FDA approval on June 21, 2019, for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women, becoming the second approved pharmacological treatment for HSDD after flibanserin (Addyi, 2015) and the first injectable melanocortin-based HSDD therapy. The approved pharmaceutical formulation is a subcutaneous injection (1.75 mg per dose) administered as needed before anticipated sexual activity.

Bremelanotide’s mechanism of action in improving sexual desire remains incompletely characterised at the mechanistic level – the FDA’s prescribing information states “the mechanism by which bremelanotide’s action on receptors translates to a clinical effect is still unknown.” Research investigations have identified MC3R and MC4R agonism in hypothalamic and limbic regions as the proposed pharmacological basis, with downstream dopaminergic pathway activation in the nucleus accumbens and related reward circuits as the probable mediator of desire-related effects.

Bremelanotide (Vyleesi, the pharmaceutical formulation) received FDA approval on June 21, 2019. Research-grade PT-141 from RCDbio is not Vyleesi, is not the pharmaceutical formulation, and is not approved or intended for any human therapeutic use. It is not a dietary supplement and is not intended for human consumption or self-administration. All RCDbio research compounds are supplied strictly for laboratory and research purposes only.

Chemical Properties

Property	Detail
Product Type	Synthetic Cyclic Heptapeptide / Melanocortin Receptor Agonist (MC4R-Selective)
Product Name	PT-141 (Bremelanotide)
Application	Scientific / Research Use Only
CAS Number	189691-06-3
Molar Mass	1025.182 g/mol
Chemical Formula	C50H68N14O10
PubChem CID	9941379
IUPAC Name	(3S,6S,9R,12S,15S,23S)-15-[(N-Acetyl-L-norleucyl)amino]-9-benzyl-6-{3-[(diaminomethylidene)amino]propyl}-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexaazacyclotricosane-23-carboxylic acid
Peptide Structure	Cyclic heptapeptide; lactam ring between Asp3 and Lys7; N-acetyl-norleucine at position 1; C-terminal free carboxylic acid
Parent Compound	Melanotan II (cyclic α-MSH analogue with C-terminal amide; CAS 121062-08-6); PT-141 removes C-terminal amide and adds free carboxyl – eliminating melanogenic activity while retaining MC4R agonism
Receptor Profile	MC4R (primary; Ki ~10 nM); MC1R, MC3R, MC5R (secondary); MC2R (lowest activity); order of potency: MC1R > MC4R > MC3R > MC5R > MC2R
Elimination Half-Life	2.7 hours (clinical pharmacokinetics; subcutaneous administration)
Bioavailability	~100% (subcutaneous injection)
FDA Approval Status	Vyleesi (bremelanotide injection, 1.75 mg/0.3 mL) – FDA approved June 21, 2019, for HSDD in premenopausal women. Research-grade PT-141 from RCDbio is NOT Vyleesi and is not approved or intended for human use.
Synonyms	Bremelanotide; PT-141; Rekynda (alternative brand); Vyleesi (pharmaceutical)
Physical Form	Lyophilized white to off-white powder
Solubility	Soluble in water; soluble in PBS and standard aqueous buffers
Storage (Lyophilized)	−20°C; sealed container; protected from light and moisture
Storage (Reconstituted)	4°C; use within 48–72 hours; avoid repeated freeze-thaw cycles
Purity	≥98% (HPLC verified, independent third-party laboratory analysis)
WADA Status	PT-141 is not explicitly named on the 2026 WADA Prohibited List for sport performance applications. As an FDA-approved pharmaceutical that can be prescribed (Vyleesi), TUE eligibility may apply for pharmaceutical formulation in specific medical contexts; research-grade material would not qualify. Verify at GlobalDRO.com before use in sport-adjacent research contexts.

How Does PT-141 Work?

PT-141 produces its biological effects through high-affinity agonism at melanocortin receptor subtypes – principally MC4R – expressed in central nervous system regions governing sexual desire, arousal, and dopaminergic reward circuits.

MC4R and MC3R CNS Pathway Activation

PT-141 binds MC4R (Ki ~10 nM competitive binding against NDP-α-MSH) and MC3R in hypothalamic and limbic brain regions. Both receptors are Gαs-coupled GPCRs that signal through adenylyl cyclase activation and cAMP/PKA downstream cascades. In hypothalamic and limbic nuclei, MC4R activation is proposed to modulate dopaminergic tone in mesolimbic reward pathways – the nucleus accumbens and ventral tegmental area – and to reduce the inhibitory serotonergic restraint on sexual desire circuits. The mechanism linking MC4R agonism to sexual desire improvement in clinical populations is proposed but not definitively established.

Central Rather Than Peripheral Mechanism

PT-141’s mechanism is fundamentally distinct from phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil) – which act peripherally on vascular smooth muscle to improve genital blood flow through NO/cGMP pathway activation. PT-141 acts centrally in the CNS to modulate the neurochemical pathways governing sexual desire and motivation, independent of direct genital stimulation or vascular effects. In clinical trials, bremelanotide improved desire-related outcomes measured by the Female Sexual Function Index (FSFI) desire domain – a subject-reported psychological measure – not vascular endpoints.

Dopamine Pathway Interactions

In preclinical rodent preparations, MC4R activation in hypothalamic regions leads to increased dopamine release in the nucleus accumbens – the primary mesolimbic reward structure. This dopaminergic response is proposed as one mechanistic basis for the desire-enhancing effects observed in clinical populations, as dopamine signalling in the nucleus accumbens is central to motivated sexual behaviour in rodent model preparations.

Melanogenic Activity – Absent in PT-141 Compared to Melanotan II

Melanotan II activates MC1R on melanocytes, producing melanin synthesis and skin pigmentation. PT-141’s structural modification (C-terminal free acid replacing C-terminal amide) significantly reduces MC1R-mediated melanogenic activity while preserving MC4R agonism – a key design improvement over Melanotan II for CNS-targeted research applications.

Key Research Findings

In preclinical and clinical research contexts, PT-141 has been associated with the following observations:

• MC4R agonism: MC4R binding affinity Ki ~10 nM in competitive binding assays; cAMP accumulation in hMC4R-expressing HEK-293 cells; consistent with potent MC4R agonism profile.
• Male rodent sexual behaviour: PT-141 (50 μg/kg intranasally or 50–500 pg/kg ICV) induced sexual arousal behaviour in male rats in preclinical preparations.
• Female rodent sexual behaviour: PT-141 (100–200 μg/kg SC or 800 μg/kg ICV) induced lordosis and sexual receptivity in female rats.
• HSDD clinical trials: In Phase 2/3 randomised clinical trials, bremelanotide 1.75 mg SC produced statistically significant improvements in FSFI desire domain scores versus placebo in premenopausal women with HSDD – supporting FDA approval as Vyleesi.
• No melanogenic activity: PT-141 does not produce significant skin tanning in clinical study populations at therapeutic doses, confirming reduced MC1R activity compared to Melanotan II.

All preclinical findings are from in vitro and rodent model data. Clinical findings relate to the pharmaceutical Vyleesi formulation at defined doses in approved clinical trial protocols. Research-grade PT-141 from RCDbio is not a pharmaceutical product. These observations do not constitute evidence of efficacy or safety for research-grade material.

What are the Potential Research Applications?

Melanocortin Receptor Pharmacology – MC4R-Selective Studies PT-141 is employed as the primary cyclic MC4R-selective reference agonist in receptor binding assays, cAMP accumulation studies, and downstream signalling characterisation at MC4R in hypothalamic, limbic, and immune cell preparations. Research examines the structural basis for MC4R selectivity relative to MC1R (melanogenic activity) across the melanocortin agonist series.

CNS Sexual Desire and Reward Circuit Research PT-141 is employed in rodent preclinical preparations to investigate melanocortin receptor-mediated modulation of mesolimbic dopamine signalling, hypothalamic appetite-sex drive interactions, and the relationship between MC4R activation and motivated sexual behaviour in controlled experimental paradigms.

Hypothalamic MC3R/MC4R and Energy Homeostasis Research MC3R and MC4R are both expressed in hypothalamic nuclei governing energy homeostasis and food intake. PT-141’s MC3R/MC4R dual agonism makes it a useful tool compound for comparative studies examining how melanocortin receptor agonism influences appetite, body weight regulation, and energy expenditure pathways alongside sexual desire circuitry.

Melanocortin System Structure-Activity Research PT-141 is positioned between Melanotan II (cyclic MC1R/MC4R agonist with tanning) and KPV (linear MC3R/MC5R anti-inflammatory fragment) in the melanocortin agonist pharmacological space. It is employed in comparative SAR studies mapping receptor subtype selectivity determinants across cyclic and linear melanocortin agonist series.

What are the Potential Side Effects?

The following observations are from the pharmaceutical Vyleesi clinical trial data.

• Nausea and vomiting – most frequently reported adverse events in clinical trial populations (approximately 40% of participants); dose-dependent; predominantly transient (onset 1 hour, resolution within 12 hours)
• Flushing – reported in approximately 20% of clinical trial participants; onset within 1 hour of injection
• Injection site reactions – erythema, bruising reported at low-to-moderate frequency
• Headache reported at low frequency
• Transient blood pressure increases – systolic BP increases of ~6 mmHg noted in clinical pharmacology studies; contraindicated in patients with high CV risk in the pharmaceutical context
• Hyperpigmentation (focal) – skin discolouration reported rarely with repeat administration, attributed to residual MC1R activity
• No human safety data has been established for research-grade PT-141 outside approved clinical trial contexts

Risk & Handling

Handling Precautions

PT-141 should only be handled by trained laboratory personnel. Appropriate PPE: nitrile gloves, lab coat, eye protection. Use in a laminar flow cabinet. Avoid aerosol generation. The cyclic lactam structure is stable but contains an indole ring (Trp) sensitive to oxidative photodegradation – protect from UV and prolonged light exposure.

Exposure Risks

Risk Tier: MODERATE

PT-141 is a potent CNS-active MC4R agonist. Accidental systemic exposure may produce nausea, flushing, blood pressure changes, and CNS melanocortin pathway activation. The 2.7-hour half-life means effects from accidental exposure would be transient but potentially significant. No human safety data for research-grade material outside clinical trial protocols.

Storage

• Lyophilized: −20°C; sealed; light-protected; desiccated
• Reconstituted: 4°C; 48–72 hours; protect from light
• Tryptophan/indole ring photosensitive – avoid UV throughout

Frequently Asked Questions

Q: What is PT-141, and how does it differ from Melanotan II? A: PT-141 (Bremelanotide) is a cyclic heptapeptide derived from Melanotan II through C-terminal modification (amide → free carboxyl). This modification significantly reduces MC1R-mediated melanogenic (tanning) activity while preserving MC4R/MC3R CNS agonism. The pharmaceutical formulation (Vyleesi) is FDA-approved for HSDD. Research-grade PT-141 from RCDbio is not Vyleesi and is not approved or intended for human use.

Q: Is PT-141 FDA-approved? A: The pharmaceutical formulation Vyleesi (bremelanotide injection, 1.75 mg/0.3 mL) was FDA-approved on June 21, 2019, for HSDD in premenopausal women. Research-grade PT-141 from RCDbio is not Vyleesi and is not the approved pharmaceutical formulation.

Q: How does PT-141 work differently from PDE-5 inhibitors? A: PDE-5 inhibitors (sildenafil, tadalafil) act peripherally on vascular smooth muscle to enhance genital blood flow through NO/cGMP pathways – a mechanical response requiring sexual stimulation. PT-141 acts centrally in the CNS through MC3R/MC4R agonism in hypothalamic and limbic regions, modulating the neurochemical basis of sexual desire – a psychological/motivational mechanism independent of genital blood flow.

Q: What are the most common adverse effects reported for Vyleesi? A: In clinical trials of pharmaceutical Vyleesi: nausea (~40% of participants), flushing (~20%), injection site reactions, headache, and transient blood pressure increase. Nausea was the primary reason for treatment discontinuation. These observations are from pharmaceutical formulation trials and should not be extrapolated to research-grade PT-141.

Q: How should PT-141 be stored? A: Lyophilized PT-141 should be stored at −20°C in a sealed, light-protected container with desiccant. Once reconstituted, store at 4°C and use within 48–72 hours. The indole ring (Trp residue) is photosensitive – protected from UV and prolonged visible light throughout handling and storage.

Related Research Compounds

• KPV – Alpha-MSH C-terminal anti-inflammatory fragment; shares the melanocortin system research context with PT-141 as a mechanistically distinct melanocortin pharmacophore from the same parent α-MSH sequence.
• Semax – ACTH(4-7) analogue investigated for MC4/MC5 receptor interactions; shares the melanocortin receptor CNS pharmacology research context with PT-141.
• VIP – 28-AA neuropeptide investigated for VPAC1/VPAC2-mediated neuromodulation; shares the hypothalamic neuroendocrine signalling and sexual behaviour circuit research context with PT-141’s CNS mechanism studies.

All products listed are for laboratory and research purposes only.

References

1. Diamond, L. E., Earle, D. C., Heiman, J. R., Rosen, R. C., Perelman, M. A., & Harning, R. (2006). An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. Journal of Sexual Medicine, 3(4), 628–638. https://pubmed.ncbi.nlm.nih.gov/16839325/
2. Clayton, A. H., Lucas, J., DeRogatis, L. R., & Jordan, R. (2022). Phase 2 randomized placebo-controlled trial of bremelanotide for female sexual dysfunction. Obstetrics & Gynaecology, 140(4), 606–616. https://pubmed.ncbi.nlm.nih.gov/36066414/
3. Kingsberg, S. A., Clayton, A. H., Portman, D., Williams, L. A., Krop, J., Jordan, R., Lucas, J., & Simon, J. A. (2019). Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder. Obstetrics & Gynaecology, 134(5), 899–908. https://pubmed.ncbi.nlm.nih.gov/31599840/
4. King, S. H., Mayorov, A. V., Balse-Srinivasan, P., Hruby, V. J., Vanderah, T. W., & Wessells, H. (2007). Melanocortin receptors, melanotropic peptides and penile erection. Current Topics in Medicinal Chemistry, 7(11), 1098–1106. https://pubmed.ncbi.nlm.nih.gov/17584143/

Disclaimer

PT-141 (Bremelanotide) is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition. Research-grade PT-141 is not Vyleesi (bremelanotide) and is not approved or intended for any human therapeutic use.

The Food and Drug Administration has approved bremelanotide as Vyleesi for HSDD in premenopausal women. Research-grade PT-141 from RCDbio is not this product. Researchers must comply with all applicable local, state, and federal laws and regulations. By purchasing, you agree to our Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.

ATTENTION: All RCDbio products are strictly for LABORATORY AND RESEARCH PURPOSES ONLY. They are not intended for human consumption, veterinary use, or any other non-research application. For queries, complaints, or support, contact support@rcdbio.co