PT-141: research reference

Describe the model before the result. A cellular signal, behavioral observation and clinical outcome are not interchangeable evidence labels.

MC4R is a Gs protein-coupled receptor expressed in hypothalamic nuclei. Its activation modulates cyclic AMP production in cellular models.

The purity value is a product-label specification, not an assay result. A batch result can only be asserted from that batch’s certificate.

These names help identify the catalog entry. A descriptive label is not evidence of efficacy, and structural identity still requires appropriate documentation.

Melanocortin analog

Reconstitution: Laboratory procedure: allow the closed vial to reach room temperature, disinfect the septum and slowly transfer the diluent against the inner wall of the vial. Do not shake; gently swirl the vial until fully dissolved. Record the volume, diluent and date in the batch log.

Storage: Sealed vial of lyophilized material: store at −20 °C, protected from light and moisture. Avoid repeated freeze-thaw cycles of reconstituted material; aliquot when the experimental design permits.

Personal protective equipment: Handle in a clean work area with a lab coat, nitrile gloves and eye protection. Dispose of vials, tips and sharps according to the laboratory waste procedure.

This bibliography spans receptor structure in vitro, rodent behavior and human trials. Structural work resolved four complexes of full-length MC4R with Gs: bound to PT-141, alpha-MSH, the analog listed here as Melanotan-1 or a nonpeptide ligand. It describes a common in vitro binding mode among the peptide ligands (34433901).

Rodent behavior experiments used ovariectomized, hormone-primed female rats controlling the pace of encounters. Appetitive behaviors—solicitation, hopping and darting—were counted separately from consummatory behavior. Direct infusions into the lateral ventricle, medial preoptic area and ventromedial hypothalamus localized effects, and microdialysis measured neurotransmitters. The reported response was selective for appetitive behavior rather than lordosis (17958619). The 2003 paper had already combined rats and nonhuman primates with neuronal-activation markers and pseudorabies-virus transsynaptic tracing (12851303).

Human research includes a crossover study of eighteen premenopausal women using vaginal photoplethysmography and 24-hour questionnaires (16839319); two randomized placebo-controlled phase 3 trials totaling 1,267 women with FSFI desire and FSDS-DAO item 13 as coprimary endpoints (31599840); and integrated safety analysis of 3,500 subjects across 43 studies (35147466). Sources: PMID 34433901; PMID 17958619; PMID 12851303; PMID 16839319; PMID 31599840; PMID 35147466.

One analytical study provides the preclinical exposure information. Ultra-high-performance liquid chromatography–tandem mass spectrometry, validated in beagle plasma, reached a 10 pg/mL lower quantification limit from 100 microliters of plasma. It used protein precipitation and verified linearity, accuracy and intra-/interday precision across the calibration range. Applied to oral exposure, it reported minimal absorption (32353679). Other cited studies used subcutaneous (31599840) or intranasal (16839319), not oral, exposure.

The references provide no measured half-life, albumin-bound fraction, metabolite identification, in vitro hepatic-fraction metabolism assay, excretion balance or lyophilized-stability study. External half-life or plasma-binding figures are not supported by this bibliography. Sources: PMID 32353679; PMID 16839319; PMID 31599840.

PT-141 is described as a synthetic alpha-MSH analog and melanocortin-receptor agonist, with MC3R and MC4R identified as predominantly central nervous system subtypes (12851303). The 2003 paper already included rats, nonhuman primates and a small adult-male series.

Its structural relationship to Melanotan-2 appears in the declared sequences: both use Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys], closed between Asp and Lys. They differ only at the C-terminus, a free acid in PT-141 and an amide in Melanotan-2, producing different molecular formulas.

The peptide’s position in full-length MC4R with Gs was resolved in vitro eighteen years later, in 2021 (34433901). The neurobiology review describes nonselective agonism across several subtypes, emphasizing MC4R and predominant expression in the hypothalamic medial preoptic area (33455598). Sources: PMID 12851303; PMID 34433901; PMID 33455598.

The catalog’s three melanocortin analogs differ along two axes: chain architecture and the receptor subtype most extensively studied for each.

Melanotan-1 is linear and thirteen residues long, with acetyl and amide termini. PT-141 and Melanotan-2 are the shorter cyclic pair, sharing a heptapeptide and Asp–Lys ring and differing only at the C-terminus. This is the catalog’s closest structural pair.

Structural work examined MC4R with alpha-MSH, PT-141 and the analog listed as Melanotan-1, placing two catalog relatives at the same subtype in vitro (34433901). The behavioral and clinical research cited here concerns PT-141 rather than the other two (17958619, 31599840). No reference tests all three in one experiment; comparison is across separate literatures. Sources: PMID 34433901; PMID 17958619; PMID 31599840.

The first gap concerns translation between models: female-rat appetitive behavior (17958619) and the foundational paper’s male-rat and primate erection findings (12851303) are not reconciled by a cited reference.

The second concerns measurement: photoplethysmographic vasocongestion did not change while reported measures did (16839319), without an explanation here. Third, phase 3 differences from placebo were statistically significant but small—0.3–0.4 points in the desire domain—and no reference establishes what scale change is perceptible (31599840).

Focal hyperpigmentation presents another tension. The integrated analysis records it as uncommon in trials but present in more than one-third of subjects after prolonged daily exposure (35147466), a finding not anticipated by the cited preclinical work. Sources: PMID 17958619; PMID 12851303; PMID 16839319; PMID 31599840; PMID 35147466.