PT-141

PT-141 Peptide

PT-141 (Bremelanotide) is a synthetic, engineered cyclic heptapeptide. Its molecular architecture is closely related to the endogenous neurohormone, alpha-melanocyte-stimulating hormone (alpha-MSH). Mechanistically, PT-141 functions as a highly selective and potent melanocortin receptor agonist, displaying strong binding affinity and biological activity primarily at the MC3R and MC4R receptor subtypes, which are prominently expressed within the central nervous system (CNS). Research applications for PT-141 are focused on discerning its crucial role in the modulation of sexual behavior, CNS signal processing, and the comprehensive regulation exerted by the central melanocortin pathway over energy homeostasis and neuroendocrine function.

A key pharmacological characteristic of PT-141 is its deliberate minimization of activity at the MC1R receptor. The MC1R subtype is the receptor primarily responsible for regulating skin and hair pigmentation. This engineered selective receptor profile establishes PT-141 as an essential, non-pigmenting experimental tool for the focused investigation of central melanocortin mechanisms related to neural activity and behavioral outcomes, without the introduction of peripheral pigmentation variables.

PT-141 Peptide Overview

PT-141 was developed through a highly focused structural modification and refinement of the known alpha-MSH analogue, Melanotan II. The strategic objective of this molecular engineering was to maximize the peptide's selectivity and pharmacological potency toward the centrally expressed melanocortin receptors (MC3R and MC4R), which are key mediators of sexual response, energy equilibrium, and appetite control.

Empirical data indicates that PT-141 exerts its primary effects by influencing the neuronal function within the hypothalamus, the brain's paramount coordination center for neuroendocrine integration. This localized action is observed to modulate several complex physiological responses, including sexual arousal mechanisms, associated behavior patterns, and the critical control over feeding and appetite.

Preclinical studies have consistently utilized PT-141 in models designed to investigate complex states such as sexual dysfunction (SD), various metabolic imbalances, and the dynamics of neuroendocrine signaling. These widespread applications confirm the compound's significance as a highly valuable research tool and reference agent for systematically dissecting the functional contributions of central melanocortin pathways in regulating both neural pathways and complex behavioral expressions.

PT-141 Peptide Structure

PT-141 is composed of a specific sequence of seven amino acid residues. This sequence is conformationally stabilized into a chemically robust cyclic structure by an internal lactam bridge, a feature vital for enhancing its metabolic half-life and optimizing its receptor binding. The precise linear amino acid sequence is defined as:

• H-Cys-Glu-His-D-Phe-Arg-Trp-Lys-OH

The definitive cyclic configuration is achieved via the formation of a covalent lactam bridge, which specifically links the side chains of the Cysteine (Cys) residue to the Lysine (Lys) residue within the peptide chain.

Structure Solution Formula (Non-Chemical Notation):

C47 H64 N14 O10 S

Molecular Weight: 991.14 g/mol

The molecular refinement process that yielded PT-141 involved the strategic removal of the C-terminal amide group present in Melanotan II. This critical structural differentiation is directly responsible for PT-141's unique pharmacological profile and its enhanced functional selectivity for central melanocortin receptors, particularly the MC4R subtype.

PT-141 Peptide Research

Melanocortin System and Sexual Function

Preclinical evidence consistently demonstrates that PT-141 acts as a powerful agonist for both MC3R and MC4R receptors located predominantly in the hypothalamus, the principal brain region mediating sexual motivation. This agonism is shown to robustly stimulate sexual arousal and promote copulatory behavior in experimental models of both sexes. A key finding is that the compound's action is mediated through a central neural pathway, establishing a clear mechanistic distinction from the peripheral vascular effects associated with phosphodiesterase type 5 inhibitors (PDE5i). This makes PT-141 an indispensable agent for fundamental research into the neuroendocrine regulation of sexual function.

Neuroendocrine and Appetite Regulation

The central melanocortin signaling network is a critical physiological system for the robust regulation of systemic energy balance and food intake. Research with PT-141 has explored its observed effects on food intake suppression and its influence on mechanisms governing weight regulation in various rodent models. These findings underscore the peptide's high relevance in studies targeting metabolic disorders and the complex, integrated functioning of neuroendocrine processes.

CNS Pharmacology and Experimental Profile

PT-141 is characterized by a favorable combination of demonstrated blood-brain barrier (BBB) permeability and a high degree of target receptor selectivity. These intrinsic properties have generated broad scientific interest in its potential applications for complex neuroendocrine and metabolic investigations. Preliminary safety assessments from controlled experimental administration studies (e.g., intranasal or subcutaneous routes) suggest a generally favorable pharmacological profile within research settings.

Key Research Areas Summary

Research Area

Primary Receptor Target(s)

Mechanism of Action

Key Experimental Observation

Sexual Arousal

MC4R (high affinity)

Central Neurochemical Stimulation

Induction of sexual motivation and behavioral response

Appetite Regulation

MC3R, MC4R

Hypothalamic Neural Modulation

Suppression of food intake; effects on energy balance

Hemorrhagic Shock

MC1R, MC4R

Anti-Ischemic and Tissue Protection

Mitigation of tissue damage following acute blood loss

Fungal Infection

MC1R

Antifungal and Anti-inflammatory Action

Research into alternative microbial control strategies

PT-141 and Sexual Arousal

PT-141 is specifically renowned for its potent and selective agonism of the MC4R receptor, a central node in the regulation of sexual motivation and behavior via CNS pathways. Experimental evidence across multiple animal models consistently confirms that MC4R activation stimulates both sexual motivation and copulatory behavior in male and female subjects. The mechanism of action is distinctly neurochemical, targeting the brain's central arousal pathways, which is fundamentally different from peripheral agents. This positions PT-141 as an invaluable research compound for studying sexual arousal disorders hypothesized to be rooted in central, neurological factors rather than primary vascular causes.

Clinical research involving men with Erectile Dysfunction (ED) who were non-responsive to sildenafil treatment found that a significant proportion achieved satisfactory sexual performance following intranasal PT-141 administration. The observation of a dose-dependent efficacy in these studies supports the compound's potential utility in cases linked to central neurobiological factors. These findings suggest PT-141 provides unique insights for research into ED and the neurological basis of low sexual desire.

PT-141 and Hemorrhage

Research initiated in 2009 led to the development of a structurally modified version of PT-141 to investigate its application in the context of acute hemorrhagic shock. Given the compound's agonistic activity at both the MC1R and MC4R receptors, it was experimentally shown to significantly reduce ischemia and provide potent tissue protective effects against oxygen deprivation resulting from severe blood loss (hypovolemic shock). Intravenous administration in research models demonstrated an overall absence of major adverse effects. A derivative compound, PL-6983, successfully advanced through Phase IIb clinical trials, confirming promising protective effects without significant observed toxicity.

PT-141 and Infection

Experimental studies utilizing rat models of fungal infection indicated that activation of the MC1R receptor by PT-141 can elicit notable antifungal and anti-inflammatory actions. This discovery is highly relevant given the limitations of current antifungal medications, which often suffer from narrow mechanisms of action and produce severe side effects that restrict long-term use. PT-141’s unique receptor-mediated activity positions it as a potential research target for developing alternative strategies against fungal infections, particularly in immunocompromised subjects where mitigating inflammation and infection-related mortality is a critical need.

Reference Citations

Citation Number

Title and Journal

PubMed Link

1

Dorr RT, et al. Melanocortin receptor agonists and sexual function: discovery of PT-141. Ann N Y Acad Sci. 2003;994:96-102.

https://pubmed.ncbi.nlm.nih.gov/12851312/

2

Shadiack AM, et al. Melanocortin receptor agonists in sexual behavior research. Brain Res. 2007;1124(1):166–175.

https://pubmed.ncbi.nlm.nih.gov/17118440/

3

Hadley ME, et al. Discovery and development of melanocortin receptor ligands. Ann N Y Acad Sci. 2006;994:1-15.

https://pubmed.ncbi.nlm.nih.gov/12851309/

4

King SH, et al. PT-141: novel melanocortin analog in sexual arousal studies. J Sex Med. 2008;5(8):1939-1948.

https://pubmed.ncbi.nlm.nih.gov/18624943/

5

Giuliano F, et al. Central melanocortin pathways and erectile function. Int J Impot Res. 2007;19(1):17–23.

https://pubmed.ncbi.nlm.nih.gov/17043692/

6

Clayton AH, et al. Bremelanotide in female sexual dysfunction studies. J Sex Med. 2016;13(5):696-706.

https://pubmed.ncbi.nlm.nih.gov/27045212/

7

Wessells H, et al. Central melanocortin modulation of sexual function in humans. J Urol. 2000;164(3 Pt 1):738-743.

https://pubmed.ncbi.nlm.nih.gov/10953129/

8

van der Ploeg LH, et al. Melanocortin receptors and obesity research. Endocr Rev. 2002;23(6):728-743.

https://pubmed.ncbi.nlm.nih.gov/12466191/

9

Kask A, et al. Melanocortins in the brain: from pigmentation to appetite. Eur J Pharmacol. 1999;375(1-3):1–12.

https://pubmed.ncbi.nlm.nih.gov/10443489/

10

Wikberg JES, et al. Five subtypes of melanocortin receptors in energy homeostasis. Peptides. 1999;20(4):401-410.

https://pubmed.ncbi.nlm.nih.gov/10328292/

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The products offered on this website are supplied exclusively for in-vitro research use. In-vitro studies (Latin: in glass) are by definition conducted outside of a living biological system. These products are not intended as medicines or drugs and have not been evaluated or approved by the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. Introduction into the body of humans or animals is strictly and legally prohibited.

STORAGE

Storage Instructions

All PT-141 product is manufactured using a specialized lyophilization (freeze-drying) process. This process is engineered to ensure the peptide's structural integrity and stability are preserved during shipping for an approximate period of 3 to 4 months.

Lyophilization, commonly known as cryodesiccation, is a sophisticated dehydration technique. The peptide solution is initially frozen solid, and then subjected to a powerful vacuum. This process forces the frozen water content to bypass the liquid phase and transition directly from a solid (ice) to a gas (vapor) through sublimation. The final product is a highly stable, white, lyophilized peptide powder. This powder remains stable for storage at ambient room temperature for a significant period until it is prepared for experimental use (reconstituted) using bacteriostatic water.

Once the peptide is reconstituted with bacteriostatic water, the resulting solution must be maintained under refrigeration (typically below 4 degrees Celsius or 39 degrees Fahrenheit) to preserve its potency. After mixing, the peptide solution typically remains stable for a period of up to 30 days.

For long-term storage extending over many months to several years, the optimal recommendation is to keep the lyophilized powder in an ultra-low temperature freezer at -80 degrees Celsius (-112 degrees Fahrenheit). Storage under these specific conditions provides the maximum level of stability and protection against molecular degradation.

Upon product receipt, it is essential that peptides are kept cool and shielded from all light exposure. For short-term use—ranging from a few days up to a few months—refrigeration below 4 degrees Celsius (39 degrees Fahrenheit) is considered sufficient. Lyophilized peptides generally maintain stability at room temperature for several weeks, which may be acceptable for brief holding periods before use.

Best Practices For Storing Peptides

Strict adherence to proper peptide storage protocols is essential for ensuring the accuracy, reliability, and reproducibility of laboratory results. Correct storage procedures are fundamental to preventing common issues like contamination, oxidation, and molecular degradation.

A summary of recommended storage conditions is:

• Upon Receipt: Peptides must be kept cool and shielded from light.
• Short-Term Storage (Days to Months): Refrigeration below 4 degrees Celsius (39 degrees Fahrenheit) is the standard.
• Long-Term Preservation (Months to Years): Storage in a freezer at -80 degrees Celsius (-112 degrees Fahrenheit) provides optimal stability.

It is critically important to minimize freeze-thaw cycles, as these rapid and repeated temperature fluctuations significantly accelerate peptide degradation. Furthermore, researchers must avoid frost-free freezers, as their automatic defrosting cycles introduce temperature variations that can compromise peptide stability.

Preventing Oxidation and Moisture Contamination

The protection of peptides from ambient air and moisture exposure is mandatory, as both are potent catalysts for chemical degradation. Moisture contamination is a high-risk factor when removing frozen vials. To prevent condensation from forming on the cold powder or container walls, researchers must always allow the sealed vial to fully equilibrate to room temperature before opening it.

Minimizing air exposure is equally vital to prevent chemical oxidation. The peptide container should remain closed as much as possible. After removing the precise amount required for the experiment, the vial must be promptly and securely resealed. For specialized long-term protection, storing the remaining peptide under a dry, inert gas atmosphere (such as nitrogen or argon) can further mitigate oxidation risks. Peptides containing cysteine (C), methionine (M), or tryptophan (W) residues are particularly susceptible to air oxidation and demand extra careful handling.

To maintain long-term stability, avoid frequent thawing and refreezing. The most effective laboratory practice is to divide the total peptide quantity into smaller, designated single-use aliquots immediately upon receipt. This method eliminates the need for repeated handling and temperature exposure of the bulk material, thereby preserving integrity over extended use.

Storing Peptides In Solution

Peptide solutions have a significantly limited shelf life compared to the lyophilized powder and are notably more susceptible to both microbial and chemical degradation. Specifically, peptide sequences that contain cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) residues are known to degrade most rapidly when dissolved.

If storage in solution is necessitated by experimental design, the use of sterile buffers with a stable pH range between 5 and 6 is highly recommended. The solution must be immediately portioned into aliquots to mitigate the damaging effects of repeated freeze-thaw cycles. Under refrigerated conditions at 4 degrees Celsius (39 degrees Fahrenheit), most peptide solutions maintain sufficient stability for up to 30 days. However, peptides with known inherent instability should be frozen when not in immediate use.

Peptide Storage Containers

Containers selected for peptide storage must be clean, chemically inert, durable, and chemically resistant. They must also be appropriately sized to minimize excess air space above the powder or solution. Both glass and specialized plastic vials are suitable options. High-quality glass vials are generally preferred for long-term storage due to their superior chemical inertness. However, peptides are often shipped in plastic to prevent breakage. Transferring the peptide to a high-quality glass vial may be advisable for very prolonged storage periods.

Peptide Storage Guidelines: General Tips

Adherence to these fundamental guidelines is mandatory to ensure peptide stability and prevent degradation:

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles to prevent structural damage.
• Minimize exposure to air to prevent chemical oxidation.
• Protect peptides from light exposure.
• Do not store peptides in solution long term; prioritize lyophilized storage.
• Pre-aliquot peptides based on experimental use to limit unnecessary handling.