PT-141

Research Overview

PT-141 serves as a valuable research tool for investigating melanocortin receptor-mediated sexual function and reproductive pathways. This synthetic peptide represents a des-acetyl metabolite of Melanotan II, arising through enzymatic deacetylation. Research applications focus on understanding MC3R/MC4R receptor roles in sexual arousal, erectile function, reproductive behavior, and central melanocortin signaling with reduced pigmentation effects compared to broader-spectrum melanocortin agonists.

The peptide’s designation as PT-141 originates from its development as Palatin Technologies compound 141, later receiving the generic name bremelanotide. PT-141 demonstrates preferential activation of MC3R and MC4R over MC1R, distinguishing it from parent compound MT-2 which activates all melanocortin receptor subtypes. This selective receptor profile enables research into MC3R/MC4R-specific effects without confounding MC1R-mediated pigmentation.

PT-141 research has contributed significantly to understanding melanocortin system roles in sexual function, particularly central nervous system pathways involved in arousal, desire, and erectile function. The peptide’s ability to induce sexual arousal effects through central mechanisms rather than peripheral vascular mechanisms distinguishes it from other research approaches to sexual function investigation.

Molecular Characteristics

Complete Specifications:

• CAS Registry Number: 189691-06-3
• Molecular Weight: 1,025.18 Da
• Molecular Formula: C₅₀H₆₈N₁₄O₁₀
• Amino Acid Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ (des-acetyl MT-2)
• PubChem CID: 9941957 (related to MT-2)
• Peptide Classification: Synthetic cyclic heptapeptide, selective MC3R/MC4R agonist
• Appearance: White to off-white lyophilized powder
• Solubility: Water, bacteriostatic water, phosphate buffered saline

The peptide’s cyclic structure forms through lactam bridge formation between the aspartic acid side chain and lysine epsilon-amino group, creating the same seven-membered ring as MT-2. PT-141 differs from MT-2 by lacking the N-terminal acetyl group, resulting from enzymatic deacetylation. This structural modification alters receptor selectivity profile, reducing MC1R activation while maintaining MC3R/MC4R agonist activity.

Pharmacokinetic Profile in Research Models

PT-141 pharmacokinetic characterization in preclinical research reveals important properties for experimental design:

Absorption and Bioavailability:

• Subcutaneous and intranasal administration routes investigated
• Enhanced stability against peptidase degradation due to cyclic structure
• Intranasal route shows rapid absorption with CNS penetration
• Subcutaneous route provides sustained absorption profile

Distribution and Elimination:

• Plasma half-life: Approximately 2-3 hours in research models
• Blood-brain barrier penetration demonstrated
• Central nervous system distribution crucial for sexual function effects
• Distribution to hypothalamic and limbic regions observed

Pharmacodynamic Characteristics:

• Onset of sexual arousal effects: 30-90 minutes post-administration in research models
• Duration of effects: 6-12 hours
• MC3R/MC4R activation in central melanocortin circuits
• Reduced melanotropic effects compared to MT-2

These pharmacokinetic properties inform research protocol design, particularly regarding route selection, timing of behavioral assessments, and measurement of central vs. peripheral effects.

Research Applications

Sexual Arousal and Reproductive Function Research

PT-141 serves as a primary research tool for investigating melanocortin-mediated sexual function:

• Central Arousal Pathway Studies: Investigation of hypothalamic and limbic system melanocortin circuits involved in sexual arousal and desire
• MC4R Sexual Function Research: Examination of MC4R receptor roles in sexual behavior, erectile function, and arousal pathways
• Neural Circuit Mapping: Studies identifying specific brain regions and neural pathways mediating PT-141’s sexual function effects
• Behavioral Assessment: Research on mating behavior, sexual motivation, copulatory behavior in animal models
• Gender-Specific Effects: Investigation of male vs. female sexual function pathways and differential melanocortin receptor roles

Research protocols employ sexual behavior assays, copulation testing, genital arousal measurements, and neural activation mapping to characterize PT-141’s effects on sexual function mechanisms.

Erectile Function Mechanism Studies

PT-141 enables investigation of central erectile function pathways:

• Central vs. Peripheral Mechanisms: Research distinguishing central arousal-mediated erection from peripheral vascular mechanisms
• Spinal Cord Pathway Research: Investigation of spinothalamic pathways and spinal reflexes involved in erectile function
• Autonomic Nervous System Studies: Examination of parasympathetic activation and neural control of penile erection
• Nitric Oxide Pathway Investigation: Research on NO-mediated vasodilation downstream of central melanocortin activation
• Erectile Dysfunction Models: Studies in various experimental models of erectile dysfunction

Laboratory investigations include penile erection monitoring, intracavernosal pressure measurements, neural pathway tracing, and neurotransmitter system studies.

Melanocortin Receptor Selectivity Research

PT-141’s altered receptor profile enables selectivity studies:

• MC3R vs. MC4R Pharmacology: Investigation of differential receptor contributions to sexual function effects
• MC1R Selectivity Research: Comparative studies with MT-2 to understand pigmentation vs. sexual function pathway separation
• Receptor Distribution Studies: Mapping of MC3R and MC4R expression in brain regions relevant to sexual function
• Signal Transduction Pathways: Analysis of cAMP signaling, MAPK activation, and downstream effects specific to MC3R/MC4R
• Structure-Activity Relationships: Research examining how structural modifications alter receptor selectivity

Research protocols include receptor binding assays, functional selectivity measurements, and comparative studies with receptor-selective compounds.

Central Melanocortin System Research

PT-141 enables broader melanocortin pathway investigation:

• Hypothalamic Circuit Research: Studies on paraventricular nucleus (PVN) and other hypothalamic regions expressing MC3R/MC4R
• Neurotransmitter Interactions: Investigation of melanocortin interactions with dopamine, oxytocin, serotonin, and other neurotransmitter systems
• Energy Homeostasis Pathways: Research examining MC4R roles in feeding behavior and energy regulation (with reduced effects compared to more selective MC4R agonists)
• Stress Response Studies: Investigation of melanocortin system involvement in stress, anxiety, and behavioral responses
• Neuropeptide Interactions: Research on melanocortin system interactions with kisspeptin, GnRH, and other reproductive neuropeptides

Studies employ neural circuit mapping, neurotransmitter measurements, electrophysiology, and behavioral pharmacology techniques.

Female Sexual Function Research

PT-141 research extends to female reproductive function:

• Female Arousal Mechanisms: Investigation of central arousal pathways in female research models
• Genital Blood Flow Research: Studies on clitoral and vaginal blood flow regulation through central pathways
• Ovarian Function Studies: Research on melanocortin receptor roles in ovarian physiology
• Reproductive Behavior: Investigation of receptivity, lordosis behavior, and mating behavior in female models
• Hormonal Interactions: Studies examining interactions with estrogen, progesterone, and other reproductive hormones

Research protocols include female sexual behavior assessments, genital blood flow measurements, and neural pathway investigations.

Laboratory Handling and Storage Protocols

Lyophilized Powder Storage:

• Store at -20°C to -80°C in original sealed vial
• Protect from light exposure (peptide is photosensitive)
• Desiccated storage environment required
• Stability data available for 12+ months at -20°C

Reconstitution Guidelines:

• Reconstitute with sterile water, bacteriostatic water (0.9% benzyl alcohol), or appropriate buffer
• Add solvent slowly down vial side to minimize foaming
• Gentle swirling motion recommended (avoid vigorous shaking)
• Allow complete dissolution before use (typically 2-3 minutes)
• Final pH should be 6.0-7.5 for optimal stability

Reconstituted Solution Storage:

• Short-term storage: 4°C for up to 7 days
• Long-term storage: -20°C in aliquots to avoid freeze-thaw cycles
• Single-use aliquots recommended to maintain peptide integrity
• Avoid repeated freeze-thaw cycles (maximum 2-3 cycles)
• Protect from light during storage and handling

Photosensitivity Considerations:
PT-141 demonstrates light sensitivity. Store in amber vials or protect from light exposure. During experimental procedures, minimize light exposure and use light-protected containers.

Quality Assurance and Analytical Testing

Each PT-141 batch undergoes comprehensive analytical characterization:

Purity Analysis:

• High-Performance Liquid Chromatography (HPLC): ≥98% purity
• Analytical method: Reversed-phase HPLC with UV detection at 280nm
• Multiple peak integration to ensure accurate purity determination

Structural Verification:

• Electrospray Ionization Mass Spectrometry (ESI-MS): Confirms molecular weight 1,025.18 Da
• Amino acid analysis: Verifies sequence composition
• Peptide content determination: Quantifies actual peptide content by weight
• Cyclization verification: Confirms proper lactam bridge formation

Contaminant Testing:

• Bacterial endotoxin: <5 EU/mg (LAL method)
• Heavy metals: Below detection limits per USP standards
• Residual solvents: TFA and acetonitrile within acceptable limits
• Water content: Karl Fischer titration (<8%)

Documentation:

• Certificate of Analysis (COA) provided with each batch
• Third-party analytical verification available upon request
• Stability data documented for recommended storage conditions
• Batch-specific QC results traceable by lot number

Research Considerations

Experimental Design Factors:

Researchers should consider several factors when designing PT-141 experiments:

1. Central vs. Peripheral Effects: PT-141’s primary mechanism involves central nervous system melanocortin activation. Experimental designs should account for CNS-mediated effects.

2. Administration Route: Route selection affects onset, duration, and intensity of effects. Intranasal administration may provide more rapid CNS penetration, while subcutaneous provides sustained effects.

3. Behavioral Timing: Sexual behavior assessments require appropriate timing relative to administration based on pharmacokinetic profile.

4. Receptor Selectivity Context: While PT-141 shows MC3R/MC4R preference, it retains some MT-2 characteristics. Consider using highly selective MC4R agonists for definitive receptor attribution studies.

5. Control Groups: Include appropriate vehicle controls, positive controls (where applicable), and comparative compounds (MT-2, selective MC4R agonists).

Mechanism Investigation:

PT-141’s mechanisms involve multiple pathways:

• MC3R/MC4R activation in hypothalamus (particularly PVN)
• Central melanocortin circuit activation
• Downstream neurotransmitter release (dopamine, oxytocin)
• Autonomic nervous system activation
• Spinal erectile centers activation
• Peripheral genital blood flow through central pathways

Secondary considerations include:

• Minimal MC1R activation (reduced pigmentation)
• Potential MC5R effects (less characterized)
• Interactions with other neuropeptide systems

Compliance and Safety Information

Regulatory Status:
PT-141 (Bremelanotide) is provided as a research chemical for in-vitro laboratory studies and preclinical research only. This product has not been approved by the FDA for over-the-counter therapeutic use, cosmetic applications, or self-administration.

Intended Use:

• In-vitro cell culture studies
• In-vivo preclinical research in approved animal models
• Laboratory investigation of melanocortin receptor pharmacology and sexual function mechanisms
• Academic and institutional research applications

NOT Intended For:

• Human consumption or self-administration
• Therapeutic treatment of sexual dysfunction
• Diagnostic purposes
• Dietary supplementation
• Veterinary therapeutic applications without appropriate oversight
• Any medical applications

Safety Protocols:
Researchers should follow standard laboratory safety practices when handling PT-141:

• Use appropriate personal protective equipment (lab coat, gloves, safety glasses)
• Handle in well-ventilated areas or fume hood
• Protect from light exposure during handling
• Follow institutional biosafety guidelines
• Dispose of waste according to local regulations for biological/chemical waste
• Consult material safety data sheet (MSDS) for additional safety information

—