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PT-141 (Bremelanotide)

PT-141 (Bremelanotide) is a synthetic cyclic heptapeptide analogue derived from Melanotan II. It functions as a non-selective agonist of melanocortin receptors and is widely employed as a mechanistic probe to investigate G-protein coupled receptor (GPCR) signaling pathways, particularly MC3R and MC4R subtypes, in central nervous system research models.

Peptide Name

Peptide Class

Synthetic Cyclic Melanocortin Analogue

Origin

Derivative of Melanotan II

Primary Res PT-141 (Bremelanotide) earch Focus:

Melanocortin Receptor Pharmacology

Form

Lyophilized Powder

Chemical Formula

C₅₀H₆₈N₁₄O₁₀

Molecular Weight

~1,025.2 g/mol

Core Scaffold

α-Melanocyte-Stimulating Hormone (α-MSH) analogue

Structure Description

Cyclic heptapeptide featuring a lactam bridge between Aspartic Acid (Asp) and Lysine (Lys) residues, conferring conformational rigidity and enhanced receptor interaction stability.

Research literature may refer to this compound interchangeably as PT-141 or Bremelanotide. Cyclic notation typically denotes the lactam bridge position (e.g., Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH).

Store powder at +4°C (short term) or -20°C (long term). Keep desiccated.

For laboratory research use only. Reconstitute using sterile bacteriostatic water consistent with established laboratory research protocols. Preparation should be performed under aseptic conditions. Reconstituted material is not intended for long-term storage.

Core Scaffold

MELANOCORTIN RECEPTOR SUBTYPE PHARMACOLOGY (MC1R–MC5R)

PT-141 acts as a non-selective agonist with varying affinities across the melanocortin receptor family. It is extensively used to profile receptor activation kinetics and downstream signaling specificity.

MC3R & MC4R:
High-affinity binding to these central nervous system receptors is the primary focus of research into metabolic regulation and behavioral signaling pathways.
MC1R:
Retains measurable binding affinity for melanocytic receptors, typically evaluated as a secondary target relative to CNS-expressed receptors.
Selectivity Profiling:
Employed in comparative assays to distinguish downstream signaling effects mediated by MC4R versus MC1R activation.

GPCR SIGNALING READOUTS & PATHWAY BIAS

As a G-protein coupled receptor (GPCR) agonist, PT-141 serves as a tool for mapping intracellular signal transduction cascades.

cAMP Accumulation:Primary readout in in-vitro assays, measuring adenylyl cyclase activation via the Gs alpha subunit.
β-Arrestin Recruitment: Investigated to assess potential biased agonism, evaluating whether PT-141 preferentially activates G-protein signaling versus receptor internalization pathways compared to endogenous α-MSH.

CNS-RELEVANT SIGNALING STUDIES (PRECLINICAL)

PT-141 is widely used as a probe to explore how melanocortin signaling interfaces with other central neurotransmitter systems in experimental models.

Dopaminergic Interaction:
Rodent studies examine downstream dopamine release within the medial preoptic area (mPOA) following MC4R activation.
Hypothalamic Activation:
Research maps neuronal activation patterns using markers such as c-Fos expression in hypothalamic nuclei associated with homeostatic and arousal signaling.

(Compliance anchor: preclinical / experimental systems only.)

MELANOCORTIN SYSTEM CROSS-REACTIVITY

Comparative ligand studies frequently evaluate PT-141 alongside related analogues (e.g., Melanotan II, HS014) to investigate receptor docking and activation requirements.

Structural Stability: The cyclic lactam bridge provides a rigid molecular scaffold, enabling evaluation of how conformational constraint influences receptor engagement relative to linear peptides.
Metabolite Analysis: Studies assess amide bond stability and potential metabolite formation in biological matrices.

RESEARCH LIMITATIONS

Receptor Desensitization: Prolonged exposure in cell culture models may induce rapid MC4R internalization and desensitization, complicating long-term signaling experiments.
Subtype Selectivity: PT-141 lacks high specificity between MC3R and MC4R, necessitating knockout models or selective antagonists to isolate receptor-specific effects.
Species Differences: Melanocortin receptor homology varies between rodents and primates, potentially affecting binding affinity and downstream signaling interpretation.

KEY SCIENTIFIC REFERENCES

Rosen, L. G., et al. (2004).
Effects of low-dose PT-141 on sexual behavior in male rats: context-dependent activity.
International Journal of Impotence Research.
Rössler, A., et al. (2006).
Pharmacokinetics of the melanocortin agonist PT-141.
European Journal of Clinical Pharmacology.
Miller, L. H., et al. (2018).
Melanocortin-4 receptor agonists in investigational research.
Expert Opinion on Investigational Drugs.Pfaus, J. G., et al. (2004).
Melanocortin receptor agonist effects in rodent models.Proceedings of the National Academy of Sciences.
Maresca, V., et al. (2015).Melanocortin receptor regulation in cellular models.
Journal of Cellular Physiology.

The compound listed below is referenced in research contexts related to the mechanisms discussed in this article.

PT-141 (Bremelanotide) is a chemical reference standard intended strictly for in-vitro and laboratory research applications (e.g., receptor binding assays, signal transduction studies, gene expression analysis). It is not a drug, dietary supplement, cosmetic, or therapeutic agent for human or animal use. It is not intended for consumption or injection. All handling must be performed by qualified professionals in a laboratory setting.

PT-141 (Bremelanotide)

Peptide Name

Peptide Class

Origin

Primary Res PT-141 (Bremelanotide) earch Focus:

Form

Chemical Formula

Molecular Weight

Core Scaffold

Structure Description

Core Scaffold

Age Verification Required

NAD+ Buffered

MOTS-c

KPV

KLOW Blend

Ipamorelin

HGH Fragment 176-191

Glutathione

GLOW Blend

GHK-Cu