PT-141
Cyclic heptapeptide derived from Melanotan II via enzymatic hydrolysis of the C-terminal amide. Selective agonist at MC3R and MC4R with minimal MC1R (melanocyte) activity — the key structural distinction from MT-II. Studied for CNS melanocortin pathway research, particularly hypothalamic and brainstem circuit modulation, independent of melanogenesis endpoints.
Mechanism of Action
PT-141 (bremelanotide) is generated by enzymatic hydrolysis of the C-terminal amide of Melanotan II (MT-II), converting the -NH2 terminus to a free carboxylic acid (-OH). This structural change, while appearing minor, produces a significant shift in melanocortin receptor selectivity: PT-141 retains high affinity at MC3R and MC4R but has substantially reduced affinity at MC1R compared to MT-II. The consequence is that PT-141 does not significantly activate the melanogenesis pathway in melanocytes, making it a preferred tool compound for studying CNS melanocortin receptor pharmacology without confounding pigmentation endpoints.
The primary research mechanism of PT-141 is MC4R agonism in CNS circuits. MC4R is expressed in the hypothalamic paraventricular nucleus (PVN), arcuate nucleus, and medial amygdala — regions studied for autonomic nervous system regulation and limbic signalling. MC4R signalling via these structures engages downstream autonomic and limbic circuits. The PVN is particularly studied because it integrates hormonal and autonomic signalling and contains MC4R-expressing neurons with projections to brainstem autonomic centres.
MC3R, which PT-141 also activates, is expressed in hypothalamic arcuate nucleus neurons and is studied for roles in energy homeostasis as a presynaptic autoreceptor modulating melanocortin neuron activity. The combined MC3R/MC4R agonism profile of PT-141 makes it a useful pharmacological tool for dissecting these complementary hypothalamic melanocortin circuit functions.
FDA approval of bremelanotide (Vyleesi, 2019) established an extensive clinical pharmacology database for the mechanism of action, pharmacokinetics, and cardiovascular pharmacology profile of this compound, which informs preclinical research design using PT-141 as a tool compound.
Key Research Findings
- MC4R expression mapping in CNS has established the neuroanatomical basis for studying PT-141 effects in hypothalamic PVN and medial amygdala autonomic signalling circuits, characterised across multiple neuroanatomy publications. Cone research group, Vanderbilt University, MC4R neuroanatomy literature.
- MC3R and MC4R agonism by bremelanotide has been studied in rodent models examining CNS autonomic circuit modulation and nervous system signalling, establishing mechanistic roles for both receptor subtypes. Molinoff et al., Annals of the New York Academy of Sciences, 2003 (PT-141 foundational pharmacology).
- Intranasal delivery pharmacokinetics were studied during early clinical development; melanocyte stimulation was minimal due to the reduced MC1R selectivity profile, confirming the melanogenesis-independent research utility of PT-141 compared to MT-II. Palatin Technologies bremelanotide clinical development literature, 2000s–2010s.
- FDA approval of bremelanotide (Vyleesi, 2019) for hypoactive sexual desire disorder established the clinical pharmacology basis and safety/cardiovascular profile; the mechanism of action is studied in preclinical models using PT-141 as a reference tool compound for MC4R CNS pathway pharmacology. U.S. FDA Vyleesi (bremelanotide) approval, 2019; Palatin Technologies Phase 3 RECONNECT trials literature.
- Transient blood pressure changes observed in clinical studies have directed preclinical research toward route-specific pharmacokinetic work, with subcutaneous vs intranasal delivery showing different cardiovascular effect profiles — relevant for route selection in preclinical research designs. Palatin Technologies bremelanotide route-of-administration cardiovascular literature.
Citations last reviewed: 1 October 2026
As Supplied by BasedPeps
Researcher FAQ
What is PT-141?
PT-141 (bremelanotide) is a cyclic heptapeptide derived from Melanotan II by enzymatic hydrolysis of the C-terminal amide. It acts as a selective agonist at MC3R and MC4R with significantly reduced MC1R activity compared to MT-II. The primary research interest is MC4R-mediated CNS pathway activation, particularly hypothalamic paraventricular nucleus and medial amygdala circuits governing autonomic signalling.
How does PT-141 differ from Melanotan 2?
The key pharmacological difference is receptor selectivity. MT-II is a broad melanocortin agonist with significant MC1R activity, making it a tool for both melanogenesis and MC4R pathway research. PT-141 (bremelanotide) has substantially reduced MC1R affinity due to its C-terminal hydroxyl (free acid) structure versus MT-II’s C-terminal amide, shifting selectivity toward MC3R and MC4R. This makes PT-141 the preferred tool compound for CNS autonomic pathway research without confounding melanogenesis endpoints.
What are the research applications of MC4R agonists?
MC4R is expressed in hypothalamic circuits including paraventricular nucleus, arcuate nucleus, and limbic system structures including medial amygdala. Research applications include: autonomic nervous system regulation studies, energy homeostasis and feeding behaviour research, and CNS signalling pathway characterisation. FDA-approved bremelanotide (Vyleesi) established extensive clinical pharmacology data for MC4R agonism that informs preclinical tool compound research using PT-141.
How is PT-141 stored and reconstituted?
Lyophilised powder is stored at −20 °C. Reconstitution in sterile bacteriostatic water is standard for research use, gently swirling until dissolved. The nasal spray formulation is pre-formulated. Reconstituted powder solution stored at 2–8 °C and used within 28 days per experimental protocol.
Does BasedPeps provide purity documentation?
Yes. Every BasedPeps lot includes a third-party Certificate of Analysis documenting HPLC purity (≥99%) and mass spectrometric identity confirmation. Certificates of Analysis are available per batch on request.
View BasedPeps PT-141
Research-grade bremelanotide. Third-party HPLC and mass spectrometry verification per lot. Certificate of Analysis available on request. Dispatched from Riga, Latvia within 24 hours.
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