Hexarelin

Research Overview

Hexarelin serves as a valuable research tool for investigating maximal growth hormone secretagogue activity and ghrelin receptor-mediated cardiovascular protection in laboratory settings. This synthetic hexapeptide represents an advancement over first-generation GHRP-6, with a methylated tryptophan residue that enhances both potency and metabolic stability. Research applications have expanded beyond GH secretion studies to encompass investigations of cardioprotection, endothelial function, and tissue-protective mechanisms activated through ghrelin receptor pathways.

The peptide’s development focused on maximizing GH-releasing potency while maintaining the metabolic stability conferred by D-amino acid incorporation. Hexarelin demonstrates the highest GH-releasing activity among GHRP compounds on a per-dose basis, making it valuable for investigating maximal GHSR-1a activation effects. Uniquely among GHRPs, Hexarelin exhibits significant cardiovascular effects that appear to be mediated through receptors distinct from GHSR-1a, including the proposed CD36 scavenger receptor pathway. Laboratory studies investigate Hexarelin’s effects on GH dynamics, cardiac function, endothelial protection, and receptor desensitization patterns.

Hexarelin research demonstrates the peptide’s exceptional potency for GH stimulation while also revealing additional biological activities. The cardiovascular protective effects observed in preclinical models have generated substantial research interest in ghrelin receptor system biology beyond GH secretion. Studies examine the peptide’s effects in cell culture systems, isolated tissue preparations, and preclinical animal models assessing both GH axis and cardiovascular outcomes.

Molecular Characteristics

Complete Specifications:

• CAS Registry Number: 140703-51-1
• Molecular Weight: 887.04 Da
• Molecular Formula: C₄₇H₅₈N₁₂O₆
• Sequence: His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂
• Peptide Classification: Synthetic hexapeptide, growth hormone secretagogue
• Appearance: White to off-white lyophilized powder
• Solubility: Water, bacteriostatic water, phosphate buffered saline

The peptide’s six-amino acid structure closely resembles GHRP-6, with the critical difference being 2-methylation of the D-tryptophan residue at position 2. This single modification significantly enhances metabolic stability and receptor binding affinity, resulting in approximately 10-fold greater GH-releasing potency compared to GHRP-6. Like GHRP-6, Hexarelin incorporates D-phenylalanine at position 5 and features C-terminal amidation (Lys-NH₂) for protease resistance. The combination of structural modifications creates the most potent GHRP for GHSR-1a activation.

Pharmacokinetic Profile in Research Models

Hexarelin pharmacokinetic characterization in preclinical research reveals important properties for experimental design:

Absorption and Half-Life:

• Plasma half-life: Approximately 70-80 minutes following IV administration
• Longer half-life than GHRP-6 due to enhanced metabolic stability
• Rapid absorption following subcutaneous administration
• Bioavailability demonstrated across multiple routes

GH Stimulation Dynamics:

• Exceptionally potent GH elevation (highest among GHRPs)
• Peak GH levels within 30-60 minutes post-administration
• Dose-dependent response with plateau at high doses
• Synergistic amplification with GHRH analogs
• Potential for receptor desensitization with chronic dosing

Cardiovascular Effects:

• Cardioprotective effects observed independent of GH elevation
• Endothelial function improvement in vascular studies
• Potential CD36 receptor-mediated effects
• Anti-inflammatory activity in cardiovascular tissue
• Effects persist beyond plasma clearance suggesting tissue binding

These pharmacokinetic characteristics inform research protocol design. The exceptional potency requires careful dose selection, while the cardiovascular effects independent of GH provide unique research opportunities for investigating ghrelin system biology beyond GH secretion.

Research Applications

Maximal GH Secretion Studies

Hexarelin serves as a research tool for investigating maximal GHSR-1a activation. Laboratory studies examine the peptide’s effects on:

• Maximum GH Release Capacity: Investigation of peak GH secretion achievable through ghrelin receptor stimulation
• GHSR-1a Receptor Pharmacology: Research on maximal receptor activation and signal transduction
• Dose-Response Characterization: Studies defining relationship between Hexarelin dose and GH output
• Receptor Desensitization Research: Investigation of GHSR-1a downregulation and tachyphylaxis with repeated dosing
• Comparative GHRP Studies: Research comparing maximal stimulation (Hexarelin) with selective stimulation (Ipamorelin)

Research protocols employ various experimental models to characterize Hexarelin’s exceptional potency and investigate mechanisms underlying maximal GH secretagogue activity.

Cardiovascular Protection Research

Substantial research focuses on cardioprotective mechanism investigation:

• Cardiac Ischemia Studies: Research on protection against ischemia-reperfusion injury in heart models
• Endothelial Function Research: Investigation of vascular endothelial protection and function improvement
• Cardioprotective Signaling: Studies examining signaling pathways mediating cardiac protection
• CD36 Receptor Investigation: Research on potential CD36-mediated cardiovascular effects
• GH-Independent Effects: Studies distinguishing cardiovascular protection from GH-mediated effects

Laboratory protocols investigate cardiovascular protection using isolated heart preparations, cardiac myocyte cultures, ischemia-reperfusion models, and vascular function assessment.

Synergistic GH Axis Research

Laboratory studies investigate Hexarelin in combination research:

• GHRH + Hexarelin Synergy: Research on maximal synergistic GH release through dual pathway activation
• Synergy Mechanisms: Studies examining signal amplification at somatotroph level
• Optimal Combination Strategies: Investigation of dose ratios and timing for maximal GH elevation
• Comparative Synergy Studies: Research comparing Hexarelin synergy with other GHRP compounds
• Pulse Amplitude Augmentation: Studies on maximal GH pulse height achievement

Experimental models include combination protocols with various GHRH analogs to characterize synergistic interactions and maximal GH stimulation capacity.

Metabolic Research Applications

Research applications extend to metabolic investigation:

• GH-Mediated Metabolic Effects: Studies on lipolysis, glucose metabolism, and protein synthesis downstream of maximal GH elevation
• IGF-1 Production Research: Investigation of maximal IGF-1 stimulation through potent GH elevation
• Body Composition Studies: Research on fat mass and lean mass changes with potent GH secretagogue treatment
• Metabolic Adaptation Investigation: Studies on metabolic responses to high-level GH axis stimulation
• Appetite Effects: Research on ghrelin-like effects on feeding behavior and energy balance

Laboratory protocols investigate metabolic outcomes using body composition assessment, metabolic rate measurement, and biochemical analysis in animal models.

Receptor Biology and Desensitization Studies

Emerging research areas include receptor regulation investigation:

• GHSR-1a Desensitization: Research on receptor downregulation, internalization, and tachyphylaxis development
• Receptor Resensitization Studies: Investigation of recovery from desensitization and optimal dosing intervals
• Receptor Expression Research: Studies on GHSR-1a expression regulation with chronic stimulation
• Alternative Receptor Pathways: Investigation of Hexarelin effects through non-GHSR-1a receptors (CD36, others)
• Tissue Distribution Studies: Research on Hexarelin binding and effects in various tissue types

Research in this area examines mechanisms of receptor regulation and investigates Hexarelin’s unique biological activities beyond GH secretion.

Laboratory Handling and Storage Protocols

Lyophilized Powder Storage:

• Store at -20°C to -80°C in original sealed vial
• Protect from light exposure and moisture
• Desiccated storage environment recommended
• Stability data available for 24+ 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 5.0-7.0 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)

Stability Considerations:
Hexarelin demonstrates excellent stability as a lyophilized powder due to D-amino acid and methylated tryptophan incorporation. The 2-methyl modification enhances metabolic stability compared to GHRP-6. Reconstituted solutions should be used within recommended timeframes.

Quality Assurance and Analytical Testing

Each Hexarelin batch undergoes comprehensive analytical characterization:

Purity Analysis:

• High-Performance Liquid Chromatography (HPLC): ≥98% purity
• Analytical method: Reversed-phase HPLC with UV detection at 214nm
• Multiple peak integration to ensure accurate purity determination

Structural Verification:

• Electrospray Ionization Mass Spectrometry (ESI-MS): Confirms molecular weight 887.04 Da
• Amino acid analysis: Verifies sequence composition including modified amino acids
• Peptide content determination: Quantifies actual peptide content by weight

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 Hexarelin experiments:

1. Exceptional Potency: Hexarelin’s high potency requires careful dose selection. Lower doses than other GHRPs may be appropriate for comparable GH elevation.

2. Desensitization Potential: Repeated dosing may lead to receptor desensitization. Consider intermittent dosing schedules and washout periods in extended studies.

3. Cardiovascular Effects: Unique cardiovascular protective effects provide research opportunities but may complicate interpretation in studies focused solely on GH effects.

4. Comparison Studies: Hexarelin enables investigation of maximal versus selective GHRP activity when compared with compounds like Ipamorelin.

5. Synergy Research: Combination with GHRH analogs produces maximal synergistic GH release, valuable for studying upper limits of GH stimulation.

Mechanism Investigation:

Hexarelin’s mechanisms include:

• Highly potent GHSR-1a (ghrelin receptor) agonism
• Gq/11-coupled signaling with maximal pathway activation
• Potential CD36 scavenger receptor activation (cardiovascular effects)
• Phospholipase C/calcium mobilization in somatotrophs
• Synergistic interaction with GHRH pathway
• GH-independent cardioprotective signaling

The peptide’s dual activity profile (maximal GH + cardiovascular protection) provides unique research opportunities.

Compliance and Safety Information

Regulatory Status:
Hexarelin 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 human therapeutic use, dietary supplementation, or medical applications.

Intended Use:

• In-vitro cell culture studies
• In-vivo preclinical research in approved animal models
• Laboratory investigation of biological mechanisms
• Academic and institutional research applications

NOT Intended For:

• Human consumption or administration
• Therapeutic treatment or diagnosis
• Dietary supplementation
• Veterinary therapeutic applications without appropriate oversight

Safety Protocols:
Researchers should follow standard laboratory safety practices when handling Hexarelin:

• Use appropriate personal protective equipment (lab coat, gloves, safety glasses)
• Handle in well-ventilated areas or fume hood
• 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

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