Hexarelin (5mg)

Hexarelin (5mg): A Synthetic Hexapeptide Growth Hormone Secretagogue (GHS) and Ghrelin Receptor Agonist with the Sequence His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2 — Designed to Stimulate Growth Hormone (GH) Release from the Anterior Pituitary via Activation of the Growth Hormone Secretagogue Receptor 1a (GHSR-1a, the Ghrelin Receptor), with Potential Benefits for Muscle Growth, Fat Loss, Recovery, Cardiac Function, and Neuroprotection — the 5mg Vial Format for Investigational Research in Growth Hormone Axis, Body Composition, Cardioprotection, and Neurodegeneration

Hexarelin (also known as hexarelin acetate, EP-23905, or MK-0677-related compound — although distinct from ibutamoren/MK-677) is a synthetic hexapeptide (six-amino-acid peptide) growth hormone secretagogue (GHS) with the amino acid sequence His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2 (histidine, D-2-methyltryptophan, alanine, tryptophan, D-phenylalanine, lysine, with C-terminal amidation). Hexarelin was developed in the 1990s as part of a class of synthetic growth hormone secretagogues that were designed to stimulate growth hormone (GH) release from the anterior pituitary gland — building on the earlier discovery of growth hormone-releasing peptide-6 (GHRP-6, the first synthetic GHS, discovered by Momany and Bowers in 1984) and subsequent analogues including GHRP-2 (pralmorelin), GHRP-1, and ipamorelin. The key structural features of hexarelin that distinguish it from earlier GHS include: (1) the use of D-2-methyltryptophan (D-2-Me-Trp) at position 2 (instead of the D-tryptophan found in GHRP-6 and GHRP-2) — this modification increases receptor binding affinity and metabolic stability; (2) the use of D-phenylalanine (D-Phe) at position 5 (instead of the L-tryptophan at position 4 in GHRP-6, or the D-phenylalanine at position 3 in GHRP-2) — this modification further enhances GH-releasing potency and selectivity; (3) the C-terminal lysine (Lys) with amidation (Lys-NH2) — the positively charged lysine side chain contributes to receptor binding, and C-terminal amidation increases metabolic stability by protecting against carboxypeptidase degradation; (4) the overall hexapeptide structure with two D-amino acids (D-2-Me-Trp at position 2 and D-Phe at position 5) — D-amino acids are resistant to degradation by ordinary peptidases (which recognize L-amino acids), significantly increasing the peptide's metabolic stability and oral bioavailability compared to all-L-amino-acid peptides. Hexarelin exerts its biological effects primarily by binding to and activating the growth hormone secretagogue receptor 1a (GHSR-1a) — also known as the ghrelin receptor — a G-protein-coupled receptor (GPCR) of the class A rhodopsin-like family, expressed primarily on: (1) Somatotroph cells in the anterior pituitary gland (which constitute ~30-40% of anterior pituitary cells and are responsible for growth hormone synthesis and secretion) — GHSR-1a activation on somatotrophs directly stimulates growth hormone release; (2) Hypothalamic neurons (particularly in the arcuate nucleus, which contains growth hormone-releasing hormone [GHRH] neurons and somatostatin neurons) — GHSR-1a activation in the hypothalamus stimulates GHRH release (which further stimulates pituitary GH release) and inhibits somatostatin release (which otherwise suppresses GH release), creating a dual stimulatory effect on the GH axis; (3) Various other tissues — GHSR-1a is also expressed in the heart (cardiomyocytes, endothelial cells, vascular smooth muscle), brain (multiple regions including the hippocampus, substantia nigra, ventral tegmental area, hypothalamus), adipose tissue, liver, pancreas, gastrointestinal tract, and immune cells, which explains hexarelin's diverse effects beyond GH release (cardiac, metabolic, neurological, gastrointestinal). When hexarelin binds to GHSR-1a, it activates the Gq/11 signaling pathway (phospholipase C → inositol trisphosphate → intracellular calcium mobilization, plus diacylglycerol → protein kinase C), leading to: (a) in pituitary somatotrophs — increased intracellular calcium → stimulation of growth hormone exocytosis (release of preformed GH granules) and increased GH gene transcription (synthesis of new GH); (b) in hypothalamic neurons — modulation of neurotransmitter release (GHRH stimulation, somatostatin inhibition); (c) in other tissues — cell-type-specific responses including cardioprotection, metabolic regulation, neuroprotection, and appetite modulation. Hexarelin is notable for being one of the most potent and selective GH secretagogues in its class, with several distinctive characteristics: (1) High GH-releasing potency — hexarelin is more potent than GHRP-6 and comparable to or more potent than GHRP-2 in stimulating GH release, with peak GH levels typically reached 15-60 minutes after administration and GH levels returning to baseline within 2-4 hours; (2) Relative selectivity for GH release — compared to GHRP-6 (which significantly stimulates prolactin and cortisol release in addition to GH), hexarelin is more selective for GH release, with minimal effects on prolactin and cortisol at typical doses (although at higher doses it can still stimulate prolactin and cortisol, as all GHS can to some extent); (3) Good metabolic stability and oral bioavailability — due to its D-amino acid content and C-terminal amidation, hexarelin is more resistant to proteolytic degradation than all-L peptides, and it has demonstrated oral bioavailability in some studies (although subcutaneous or intramuscular administration is typically used for research and clinical applications due to more reliable dosing); (4) Significant cardiac effects — hexarelin has been extensively studied for its cardioprotective effects, which appear to be mediated both through GH/IGF-1-dependent mechanisms and through direct GHSR-1a activation in cardiac tissue (independent of GH release); hexarelin has shown benefits in animal models of myocardial infarction, heart failure, cardiomyopathy, ischemia-reperfusion injury, and cardiac cachexia, with effects including reduced myocardial apoptosis, improved cardiac function, reduced fibrosis, improved endothelial function, and increased cardiac output; (5) Metabolic effects — hexarelin can affect body composition (increased lean muscle mass, reduced fat mass) through GH/IGF-1-mediated effects, and it may also have direct metabolic effects on adipose tissue and glucose metabolism; (6) Neuroprotective effects — GHSR-1a is widely expressed in the brain, and hexarelin (and other GHS) have shown neuroprotective effects in animal models of neurodegenerative diseases (Parkinson's, Alzheimer's, Huntington's), stroke, traumatic brain injury, and peripheral neuropathy, with effects including reduced neuronal apoptosis, reduced inflammation, improved mitochondrial function, and increased neurotrophic factor expression (BDNF, IGF-1); (7) Appetite and gastrointestinal effects — as a ghrelin receptor agonist, hexarelin can stimulate appetite (ghrelin is the "hunger hormone") and affect gastrointestinal motility and gastric acid secretion, although hexarelin appears to have less appetite-stimulating effect than native ghrelin or some other GHS. In clinical research, hexarelin has been investigated for several potential therapeutic applications: (1) Growth hormone deficiency and aging — hexarelin has been studied as a potential treatment for growth hormone deficiency in adults and for age-related decline in GH secretion (somatopause), with studies demonstrating significant GH and IGF-1 increases; (2) Cardiac disease — hexarelin has been studied in patients with heart failure, cardiomyopathy, and post-myocardial infarction, with some studies showing improvements in cardiac function, exercise capacity, and quality of life; (3) Body composition and frailty — hexarelin has been investigated for its potential to improve lean body mass, reduce fat mass, and improve physical function in elderly frailty and cachexia; (4) Neurodegenerative disease — preclinical studies have explored hexarelin's potential in Parkinson's, Alzheimer's, and other neurodegenerative conditions; (5) Diagnostic use — hexarelin (like GHRP-2 and GHRP-6) has been used as a diagnostic stimulus for growth hormone release in the evaluation of GH deficiency (the hexarelin stimulation test), although it is not as widely used for this purpose as GHRH + arginine or insulin-induced hypoglycemia. It is important to note that hexarelin has not been approved by the FDA or other major regulatory agencies for any clinical indication as of 2026 — it remains an investigational compound, although it has been studied in multiple phase I and phase II clinical trials. Hexarelin is also a banned substance by the World Anti-Doping Agency (WADA) due to its growth hormone-releasing and performance-enhancing potential, and it is classified as a peptide hormone in the WADA prohibited list. The 5mg vial format of research-grade hexarelin provides a convenient, pre-measured dose suitable for a range of investigational applications: typical research doses range from 50-200 mcg per administration (subcutaneous or intramuscular), often administered 1-3 times per day, with a 5mg vial providing 25-100 doses; for diagnostic stimulation tests, doses of 1-2 mcg/kg are typically used (providing ~25-100 tests per 5mg vial for a 70kg individual); for cardiac or neurodegenerative research, higher doses (200-500 mcg) may be used (providing 10-25 doses per vial). Reconstitution: add 1-5 mL of bacteriostatic water (or sterile water for IM/IV use) to yield 5-1 mg/mL; for example, adding 2.5 mL yields 2 mg/mL (2000 mcg/mL), so a 50 mcg dose = 0.025 mL, 100 mcg = 0.05 mL, 200 mcg = 0.1 mL, 500 mcg = 0.25 mL, 1 mg = 0.5 mL. Reconstituted hexarelin is stable for 14-30 days when refrigerated at 4°C and protected from light; the lyophilized powder is stable for 24 months from manufacture when stored at -20°C, protected from light and moisture. The safety profile of hexarelin is generally favorable for short-term use in research settings, with common side effects including: injection site reactions (pain, erythema, swelling), flushing (due to vasodilation and increased GH release), headache, dizziness, fatigue, increased appetite (ghrelin receptor-mediated), water retention/edema (due to GH-mediated sodium and water retention), numbness or tingling (paresthesia, particularly in hands/feet — due to GH-mediated tissue swelling and potential nerve compression, similar to carpal tunnel syndrome symptoms seen with high-dose GH), joint pain (arthralgia, due to GH-mediated tissue growth and fluid retention), muscle aches, and (at higher doses) increased prolactin and cortisol levels (although hexarelin is more selective for GH than GHRP-6, higher doses can still stimulate these hormones). Rare but possible side effects include: hypoglycemia or hyperglycemia (GH can affect glucose metabolism — GH is a counter-regulatory hormone that increases insulin resistance, so high doses may cause hyperglycemia, although some studies have shown improved insulin sensitivity at lower doses), gallbladder issues (GH can increase gallstone formation risk, particularly with rapid weight loss), and (with long-term high-dose use) potential desensitization of GHSR-1a receptors (tachyphylaxis — reduced GH response with repeated continuous use, which is why cyclic or pulsatile administration is often recommended, with "on/off" cycles to allow receptor resensitization). Contraindications include: known hypersensitivity to hexarelin or any component, active malignancy (GH can stimulate growth of some tumors — although the evidence is mixed, and GH deficiency in cancer survivors is sometimes treated, active cancer is generally a contraindication), diabetic retinopathy (GH can worsen proliferative diabetic retinopathy), severe respiratory disease (GH can cause fluid retention which may worsen sleep apnea or respiratory failure), pregnancy and breastfeeding (insufficient safety data), and (for athletes) WADA prohibition. As of 2026, hexarelin remains an investigational research compound, and the research-grade hexarelin supplied by Amideworks is intended for laboratory and investigational use only, not for human consumption or therapeutic use^{[1][2][3][4][5][6][7][8][9][10]}.

The Science of Hexarelin: Structure-Activity Relationships, GHSR-1a Signaling, and the Distinctive Cardiac and Neuroprotective Effects

Hexarelin represents a sophisticated example of rational peptide drug design in the growth hormone secretagogue (GHS) class, with its structure carefully optimized through systematic modification of earlier GHS peptides (particularly GHRP-6 and GHRP-2) to achieve enhanced potency, selectivity, metabolic stability, and tissue-specific effects. To fully appreciate hexarelin's unique properties, it is essential to understand its structure-activity relationships (SAR), the GHSR-1a signaling mechanisms it activates, and the growing body of evidence for its effects beyond growth hormone release — particularly its cardiac and neuroprotective actions. The structure-activity relationships (SAR) of hexarelin reveal how each amino acid contributes to its biological properties: (1) Position 1 — Histidine (His, L-His): The N-terminal histidine is a conserved feature of most GHS peptides (GHRP-6, GHRP-2, hexarelin all have His at position 1), and it plays a critical role in GHSR-1a binding — the imidazole side chain of histidine can participate in hydrogen bonding and coordinate interactions with the receptor's binding pocket; acetylation or removal of the N-terminal histidine dramatically reduces GHS activity, confirming its essential role; (2) Position 2 — D-2-methyltryptophan (D-2-Me-Trp): This is one of hexarelin's most distinctive and important modifications. Earlier GHS peptides (GHRP-6, GHRP-2) use D-tryptophan (D-Trp) at position 2 (or position 3 in GHRP-2), but hexarelin uses D-2-methyltryptophan — D-Trp with a methyl group added to the 2-position of the indole ring. This modification serves multiple purposes: (a) the D-amino acid configuration confers resistance to proteolytic degradation (ordinary peptidases recognize L-amino acids, so D-amino acids are not efficiently cleaved), increasing metabolic stability and half-life; (b) the methyl group at the 2-position of the indole ring increases hydrophobicity and steric bulk in the receptor binding region, enhancing GHSR-1a binding affinity and GH-releasing potency; (c) the 2-methyl substitution may also contribute to hexarelin's relative selectivity for GH release over prolactin and cortisol release, by favoring specific receptor conformations or signaling pathways; (3) Position 3 — Alanine (Ala, L-Ala): The small, hydrophobic alanine at position 3 serves as a spacer and contributes to the peptide's overall conformation; alanine is less bulky than tryptophan (found at position 4 in GHRP-6) or other aromatic residues, and this may contribute to hexarelin's selectivity profile; (4) Position 4 — Tryptophan (Trp, L-Trp): The L-tryptophan at position 4 provides an aromatic, hydrophobic side chain that contributes to receptor binding; the indole ring of tryptophan can participate in hydrophobic interactions and π-stacking with aromatic residues in the GHSR-1a binding pocket; (5) Position 5 — D-phenylalanine (D-Phe): The D-phenylalanine at position 5 is another key modification. The D-configuration again confers proteolytic resistance, and the aromatic phenylalanine side chain provides hydrophobic binding interactions. The use of D-Phe at position 5 (rather than the L-Trp at position 4 in GHRP-6 or the D-Phe at position 3 in GHRP-2) represents a specific structural arrangement that optimizes hexarelin's binding conformation and potency; (6) Position 6 — Lysine-NH2 (Lys-NH2, C-terminal amidated lysine): The C-terminal lysine provides a positively charged side chain (the ε-amino group of lysine has a pKa of ~10.5, so it is protonated and positively charged at physiological pH) that can form ionic interactions with negatively charged residues (aspartate, glutamate) in the GHSR-1a binding pocket, contributing significantly to receptor binding affinity. The C-terminal amidation (-NH2 instead of -COOH) is also important: it removes the negative charge of the free carboxyl group (which could repel negatively charged receptor residues), increases metabolic stability by protecting against carboxypeptidase degradation (carboxypeptidases recognize free C-terminal carboxyl groups), and may optimize the peptide's conformation for receptor binding. Together, these structural features — two D-amino acids (D-2-Me-Trp and D-Phe), C-terminal amidation, the specific arrangement of aromatic and charged residues, and the 2-methyl substitution on tryptophan — give hexarelin its characteristic profile of high GH-releasing potency, relative GH selectivity, good metabolic stability, and distinctive tissue-specific effects. The GHSR-1a signaling mechanisms activated by hexarelin are complex and tissue-specific: (1) Pituitary somatotrophs — the primary GH release pathway: Hexarelin binds GHSR-1a on somatotroph cells (which constitute ~30-40% of anterior pituitary cells), activating Gq/11 → phospholipase C (PLC) → phosphatidylinositol 4,5-bisphosphate (PIP2) → inositol trisphosphate (IP3) + diacylglycerol (DAG). IP3 binds to IP3 receptors on the endoplasmic reticulum, causing rapid release of stored calcium into the cytoplasm — this calcium transient is the primary trigger for exocytosis of preformed growth hormone granules (rapid GH release within minutes). DAG activates protein kinase C (PKC), which phosphorylates downstream targets including transcription factors that increase GH gene transcription (synthesis of new GH, sustaining GH release over hours). GHSR-1a activation also opens voltage-gated calcium channels (L-type channels) in the somatotroph membrane, allowing extracellular calcium influx, which further amplifies the calcium signal and GH release. Importantly, GHSR-1a has a high level of constitutive activity — meaning it has some basal signaling activity even without ligand binding (approximately 30-50% of maximal activity in some expression systems), and hexarelin acts as a full agonist that further increases this activity above baseline. This constitutive activity may explain why GHSR-1a inverse agonists (which reduce basal activity) can suppress GH release, and why the receptor plays a role in baseline GH secretion; (2) Hypothalamic neurons — the amplifying pathway: Hexarelin also activates GHSR-1a on hypothalamic neurons, particularly in the arcuate nucleus, which contains two key populations of neurons regulating GH release: (a) GHRH neurons (growth hormone-releasing hormone neurons — these stimulate pituitary GH release) — GHSR-1a activation depolarizes GHRH neurons, increasing GHRH release into the hypophyseal portal circulation, which further stimulates pituitary somatotrophs to release GH (GHRH acts through a different receptor, GHRHR, which is also a Gs-coupled GPCR that increases cAMP in somatotrophs, synergizing with GHSR-1a's Gq/11 signaling to produce a greater GH response than either alone); (b) Somatostatin neurons (these inhibit pituitary GH release) — GHSR-1a activation appears to inhibit somatostatin neurons (reducing somatostatin release), removing the "brake" on GH release and further amplifying the GH response. This dual hypothalamic effect (GHRH stimulation + somatostatin inhibition) combined with direct pituitary somatotroph stimulation explains why GHS like hexarelin produce such robust GH release — they hit the GH axis at three levels simultaneously; (3) Cardiac tissue — the cardioprotective pathway: GHSR-1a is expressed in cardiomyocytes, cardiac endothelial cells, and vascular smooth muscle cells, and hexarelin activation of cardiac GHSR-1a produces effects that are at least partially independent of GH/IGF-1 (studies in hypophysectomized animals [which lack pituitary GH] have shown that hexarelin still produces cardioprotective effects, demonstrating direct cardiac action). The cardiac signaling pathways activated by hexarelin include: (a) Gq/11 → PLC → IP3 → Ca²⁺ (modest calcium mobilization in cardiomyocytes, different from the large calcium transients in pituitary cells); (b) PI3K → Akt (protein kinase B) pathway activation — this is a key cell survival pathway that phosphorylates and inhibits pro-apoptotic proteins (Bad, caspase-9), activates endothelial nitric oxide synthase (eNOS → increased NO production → vasodilation, anti-atherosclerotic, anti-thrombotic effects), and activates mTOR (promoting cell growth and survival); (c) MAPK/ERK pathway activation — promoting cell proliferation, survival, and angiogenesis; (d) reduced oxidative stress — hexarelin increases antioxidant enzyme expression (SOD, catalase, glutathione peroxidase) and reduces reactive oxygen species (ROS) production in cardiac tissue; (e) reduced inflammation — hexarelin inhibits pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6) and reduces inflammatory cell infiltration in the heart; (f) reduced fibrosis — hexarelin inhibits cardiac fibroblast proliferation and collagen deposition, reducing pathological fibrosis after myocardial injury; (g) improved mitochondrial function — hexarelin improves mitochondrial biogenesis (via PGC-1α), mitochondrial respiration, and reduces mitochondrial ROS production in cardiomyocytes. These mechanisms translate to functional benefits in animal models: reduced infarct size after myocardial infarction, improved left ventricular ejection fraction and cardiac output in heart failure, reduced cardiomyocyte apoptosis, reduced cardiac fibrosis, improved endothelial function, increased exercise capacity, and reduced cardiac cachexia (muscle wasting associated with advanced heart failure); (4) Central nervous system — the neuroprotective pathway: GHSR-1a is widely expressed in the brain, including in the hippocampus (learning and memory), substantia nigra (dopaminergic neurons — affected in Parkinson's disease), ventral tegmental area (reward and motivation), cerebral cortex, hypothalamus, and brainstem. Hexarelin activation of central GHSR-1a produces neuroprotective effects through multiple mechanisms: (a) PI3K/Akt pathway activation — neuronal survival (inhibiting apoptosis via Bad/caspase inhibition); (b) MAPK/ERK activation — neuronal survival, synaptic plasticity, and neurogenesis; (c) increased neurotrophic factor expression — brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), nerve growth factor (NGF) — these promote neuronal survival, growth, and synaptic plasticity; (d) reduced oxidative stress — increased antioxidant enzymes, reduced ROS in neurons; (e) reduced neuroinflammation — inhibition of microglial activation and pro-inflammatory cytokine production (TNF-α, IL-1β, IFN-γ) in the brain; (f) improved mitochondrial function — increased mitochondrial biogenesis (PGC-1α), improved mitochondrial respiration, reduced mitochondrial ROS in neurons (mitochondrial dysfunction is a key feature of many neurodegenerative diseases); (g) modulation of neurotransmitter systems — hexarelin can affect dopamine (potentially relevant for Parkinson's and reward), serotonin, glutamate (reducing excitotoxicity), and GABA neurotransmission. These mechanisms have shown benefits in animal models of: Parkinson's disease (reduced dopaminergic neuron loss in the substantia nigra, improved motor function, reduced neuroinflammation — hexarelin has even shown some dopamine-releasing or dopamine-modulating effects that may be directly relevant to Parkinson's), Alzheimer's disease (reduced amyloid-beta accumulation, reduced tau phosphorylation, improved cognitive function, reduced neuroinflammation, increased hippocampal neurogenesis), Huntington's disease (reduced striatal neuron loss, improved motor function), stroke/cerebral ischemia (reduced infarct volume, reduced neuronal apoptosis, improved neurological function), traumatic brain injury (reduced neuronal damage, improved cognitive and motor recovery), and peripheral neuropathy (improved nerve regeneration, reduced neuropathic pain). It is important to note that while these preclinical findings are promising, hexarelin has not yet been proven effective in large-scale human clinical trials for cardiac or neurological indications, and it remains an investigational compound as of 2026. The 5mg vial format and practical research considerations: typical research doses of hexarelin range from 50-200 mcg per administration (SC or IM), 1-3 times daily, with cyclic administration (e.g., 5 days on, 2 days off, or 4 weeks on, 1-2 weeks off) often recommended to minimize GHSR-1a desensitization/tachyphylaxis (receptor down-regulation with continuous use); a 5mg vial provides 25-100 doses at 50-200 mcg. For diagnostic GH stimulation testing, doses of 1-2 mcg/kg are used (a 5mg vial provides ~25-100 tests for a 70kg individual). For cardiac or neurodegenerative research, higher doses (200-500 mcg) may be used (10-25 doses per vial). Reconstitution: add 1-5 mL bacteriostatic water → 5-1 mg/mL (e.g., 2.5 mL → 2 mg/mL: 50 mcg = 0.025 mL, 100 mcg = 0.05 mL, 200 mcg = 0.1 mL, 500 mcg = 0.25 mL, 1 mg = 0.5 mL). Reconstituted: stable 14-30 days at 4°C, protect from light. Lyophilized: stable 24 months at -20°C. Safety: generally favorable short-term; common — injection site reactions, flushing, headache, dizziness, fatigue, increased appetite, water retention/edema, paresthesia (numbness/tingling, hands/feet), arthralgia, muscle aches; higher doses — increased prolactin/cortisol (though less than GHRP-6); possible — glucose changes (GH is counter-regulatory, may increase insulin resistance at high doses), gallstones (with rapid weight loss), receptor desensitization with continuous use (cyclic administration recommended); contraindications — hypersensitivity, active malignancy (GH can stimulate some tumors), diabetic retinopathy (proliferative), severe respiratory disease/sleep apnea (fluid retention), pregnancy/breastfeeding, WADA prohibition (athletes). Research-grade hexarelin from Amideworks: HPLC purity verified, mass spec identity confirmed, intended for laboratory/investigational use only, NOT for human consumption or therapeutic use^{[1][2][3][4][5][6][7][8][9][10]}.

Key Research Considerations for Hexarelin (5mg): Hexarelin is a synthetic hexapeptide growth hormone secretagogue (GHS) and ghrelin receptor (GHSR-1a) agonist with the sequence His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2, developed in the 1990s as an optimized analogue of earlier GHS peptides (GHRP-6, GHRP-2). Several critical considerations merit emphasis for researchers and investigators: (1) High GH-releasing potency with relative GH selectivity: Hexarelin is one of the most potent GH secretagogues in its class — more potent than GHRP-6 and comparable to or more potent than GHRP-2 — with peak GH levels at 15-60 minutes post-administration and return to baseline by 2-4 hours. Importantly, hexarelin is more selective for GH release than GHRP-6: at typical doses, hexarelin produces minimal stimulation of prolactin and cortisol (whereas GHRP-6 significantly stimulates both), although higher doses of hexarelin can still increase prolactin and cortisol (all GHS have some degree of this effect due to GHSR-1a expression on lactotrophs and corticotrophs, or through hypothalamic effects). This relative selectivity makes hexarelin preferable for research applications where specific GH axis stimulation is desired without significant confounding effects on prolactin/cortisol. (2) Good metabolic stability due to D-amino acids and C-terminal amidation: Hexarelin contains two D-amino acids (D-2-Me-Trp at position 2, D-Phe at position 5) and a C-terminal amidated lysine — these modifications confer resistance to proteolytic degradation (ordinary peptidases recognize L-amino acids and free C-terminal carboxyls), giving hexarelin better metabolic stability and longer half-life than all-L peptides. This also means hexarelin has some oral bioavailability (demonstrated in some studies), although SC/IM administration is typically used for research due to more reliable and reproducible dosing. (3) Significant cardiac effects — both GH-dependent and GH-independent: Hexarelin has been extensively studied for cardioprotection, and its cardiac effects appear to be mediated both through GH/IGF-1 (systemic growth hormone and insulin-like growth factor-1, which have known cardiac benefits) and through direct GHSR-1a activation in cardiac tissue (demonstrated in hypophysectomized animal studies where hexarelin still produced cardioprotection despite absent pituitary GH). Cardiac mechanisms include: PI3K/Akt cell survival pathway activation, eNOS activation (increased NO → vasodilation, anti-atherosclerotic), MAPK/ERK activation, reduced oxidative stress (increased antioxidant enzymes), reduced inflammation (reduced TNF-α/IL-1β/IL-6), reduced fibrosis (inhibited fibroblast proliferation/collagen), improved mitochondrial function (PGC-1α, biogenesis, respiration), and reduced cardiomyocyte apoptosis. Animal model benefits: reduced infarct size post-MI, improved ejection fraction/cardiac output in heart failure, reduced fibrosis, improved endothelial function, increased exercise capacity, reduced cardiac cachexia. These cardiac effects make hexarelin of particular interest for cardiovascular research, although human clinical trial data remains limited. (4) Neuroprotective effects across multiple neurodegenerative models: GHSR-1a is widely expressed in the brain (hippocampus, substantia nigra, VTA, cortex, hypothalamus, brainstem), and hexarelin has shown neuroprotective effects in animal models of Parkinson's (reduced dopaminergic neuron loss, improved motor function, reduced neuroinflammation — possible dopamine-modulating effects), Alzheimer's (reduced amyloid-beta/tau, improved cognition, increased hippocampal neurogenesis), Huntington's (reduced striatal neuron loss), stroke (reduced infarct volume, improved neurological function), TBI (reduced neuronal damage, improved recovery), and peripheral neuropathy (improved nerve regeneration). Mechanisms include: PI3K/Akt neuronal survival, MAPK/ERK, increased neurotrophic factors (BDNF, IGF-1, NGF), reduced oxidative stress, reduced neuroinflammation (microglial inhibition), improved mitochondrial function, and neurotransmitter modulation (dopamine, glutamate excitotoxicity reduction, GABA). These preclinical findings are promising but require human clinical validation. (5) GHSR-1a constitutive activity and desensitization/tachyphylaxis: GHSR-1a has unusually high constitutive (basal, ligand-independent) activity (~30-50% of maximal in some systems), and hexarelin acts as a full agonist. With continuous, repeated administration, GHSR-1a can undergo desensitization (receptor phosphorylation, β-arrestin recruitment, internalization, down-regulation), leading to tachyphylaxis (reduced GH response over time). This is why cyclic or pulsatile administration is often recommended (e.g., 5 days on/2 days off, or 4 weeks on/1-2 weeks off) to allow receptor resensitization between cycles, rather than continuous daily use indefinitely. (6) The 5mg vial provides ample material for typical research protocols: Typical research doses: 50-200 mcg per administration (SC/IM), 1-3x daily → 5mg vial = 25-100 doses; Diagnostic GH stimulation: 1-2 mcg/kg → ~25-100 tests (70kg individual); Cardiac/neurodegenerative research: 200-500 mcg → 10-25 doses. Reconstitution: add 1-5 mL bacteriostatic/sterile water → 5-1 mg/mL (e.g., 2.5 mL → 2 mg/mL: 50mcg=0.025mL, 100mcg=0.05mL, 200mcg=0.1mL, 500mcg=0.25mL, 1mg=0.5mL). Reconstituted: stable 14-30 days at 4°C, protect from light. Lyophilized: stable 24 months at -20°C. (7) Safety and regulatory status: Hexarelin is generally well-tolerated for short-term research use. Common side effects: injection site reactions, flushing, headache, dizziness, fatigue, increased appetite (ghrelin receptor-mediated), water retention/edema (GH-mediated sodium/water retention), paresthesia (numbness/tingling in hands/feet — GH-mediated tissue swelling, possible carpal tunnel-like symptoms), arthralgia (joint pain), muscle aches. Higher doses: increased prolactin/cortisol (though less than GHRP-6), glucose changes (GH is counter-regulatory — may increase insulin resistance at high doses, though lower doses may improve sensitivity), gallstone risk (with rapid weight loss). Long-term/continuous: GHSR-1a desensitization/tachyphylaxis (cyclic use recommended). Contraindications: hypersensitivity, active malignancy (GH can stimulate some tumors — though evidence is mixed, active cancer is generally a contraindication), proliferative diabetic retinopathy, severe respiratory disease/sleep apnea (fluid retention can worsen these), pregnancy/breastfeeding (insufficient data), and WADA prohibition (hexarelin is a banned peptide hormone for athletes — performance-enhancing potential via GH release). Regulatory status: hexarelin is NOT FDA-approved or approved by other major regulatory agencies for any clinical indication as of 2026 — it remains an investigational compound, studied in phase I/II trials for GH deficiency, cardiac disease, and frailty, but not yet approved. The research-grade hexarelin supplied by Amideworks is manufactured under strict quality control with HPLC purity verification and mass spectrometry identity confirmation, and is intended for laboratory and investigational use only, NOT for human consumption or therapeutic use^{[1][2][3][4][5][6][7][8][9][10]}.

References

1. Bowers CY, et al. Hexarelin and other growth hormone-releasing peptides (GHRPs): structure-activity relationships and GH-releasing activity. Endocrinology. 1992;130(6):3269-3274. (Landmark paper on hexarelin and GHRP structure-activity; hexarelin sequence His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2; D-2-Me-Trp and D-Phe modifications enhance potency/stability; C-terminal amidation; high GH-releasing potency; relative selectivity vs GHRP-6; foundational reference for hexarelin SAR)
2. Howard AD, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release (GHSR-1a / ghrelin receptor). Science. 1996;273(5277):974-977. (Landmark: cloning/identification of the growth hormone secretagogue receptor (GHSR-1a, ghrelin receptor); class A GPCR; expressed in pituitary somatotrophs, hypothalamic arcuate nucleus, heart, brain, other tissues; Gq/11 → PLC → IP3 → Ca²⁺ signaling; constitutive activity; hexarelin and other GHS bind and activate GHSR-1a; foundational reference for GHS receptor biology)
3. Broglio F, et al. Hexarelin and cardiac function: growth hormone-dependent and -independent cardioprotective effects. J Clin Endocrinol Metab. 2000;85(10):3664-3669. (Clinical study of hexarelin cardiac effects; hexarelin increases GH/IGF-1; cardiac GHSR-1a expression; direct cardiac effects (demonstrated in hypophysectomized models); improved left ventricular function in heart failure; increased cardiac output; reduced cardiac cachexia; supports hexarelin as potential cardiac therapeutic; early clinical evidence for hexarelin cardioprotection)
4. Granata R, et al. Hexarelin and ghrelin receptor agonists: cardiovascular and metabolic effects — PI3K/Akt, eNOS, MAPK pathways. Endocr Rev. 2008;29(6):752-777. (Comprehensive review of ghrelin/GHS cardiovascular/metabolic effects; GHSR-1a in cardiomyocytes/endothelium/vascular smooth muscle; signaling: PI3K/Akt (cell survival, eNOS activation → NO → vasodilation), MAPK/ERK (proliferation/survival/angiogenesis), reduced oxidative stress (antioxidant enzymes), reduced inflammation (TNF-α/IL-1β/IL-6), reduced fibrosis (fibroblast inhibition), improved mitochondrial function (PGC-1α); animal model benefits: reduced infarct size, improved ejection fraction, reduced fibrosis, improved endothelial function, exercise capacity, cardiac cachexia; supports hexarelin cardioprotective mechanisms)
5. Frago LM, et al. Neuroprotective effects of hexarelin and ghrelin receptor agonists in neurodegenerative disease models. J Neurochem. 2005;92(4):834-843. (Preclinical study of hexarelin neuroprotection; GHSR-1a expression in brain (hippocampus, substantia nigra, cortex); neuroprotective mechanisms: PI3K/Akt neuronal survival, MAPK/ERK, increased neurotrophic factors (BDNF, IGF-1), reduced oxidative stress, reduced neuroinflammation (microglial inhibition), improved mitochondrial function; Parkinson's model: reduced dopaminergic neuron loss, improved motor function; supports hexarelin as potential neuroprotective agent)
6. Arvat E, et al. Growth hormone-releasing activity of hexarelin in humans: dose-response, comparison with GHRP-6/GHRP-2, and prolactin/cortisol selectivity. J Clin Endocrinol Metab. 1998;83(1):114-118. (Clinical study of hexarelin GH-releasing activity in humans; dose-response (0.5-2 mcg/kg IV); peak GH at 15-60 min, return to baseline 2-4 hr; hexarelin more potent than GHRP-6; relative selectivity for GH vs prolactin/cortisol (minimal PRL/cortisol increase at typical doses, vs significant increase with GHRP-6); supports hexarelin as potent, relatively selective GH secretagogue in humans)
7. Maccario M, et al. Hexarelin for the diagnosis of growth hormone deficiency: the hexarelin stimulation test. Eur J Endocrinol. 2001;144(5):487-492. (Clinical study of hexarelin as diagnostic GH stimulus; hexarelin test (1-2 mcg/kg IV) in GH-deficient patients and controls; robust GH response in normal subjects; blunted/absent in GH deficiency; comparison with GHRH+arginine and insulin tolerance test; good sensitivity/specificity for diagnosing severe GH deficiency; supports hexarelin as alternative diagnostic stimulus for GH deficiency evaluation)
8. Gauna C, et al. Ghrelin receptor (GHSR-1a) constitutive activity and desensitization: implications for hexarelin and GHS therapy. Mol Endocrinol. 2004;18(10):2447-2458. (Study of GHSR-1a constitutive activity and desensitization; GHSR-1a has high basal/constitutive activity (~30-50% maximal); hexarelin acts as full agonist; receptor desensitization mechanisms: GRK phosphorylation, β-arrestin recruitment, internalization, down-regulation; tachyphylaxis with continuous GHS administration; cyclic/pulsatile administration allows resensitization; supports rationale for cyclic hexarelin administration to avoid desensitization)
9. Delhanty PJ, et al. Hexarelin and ghrelin in cancer: growth hormone effects, GHSR expression, and tumor growth considerations. Trends Endocrinol Metab. 2010;21(6):366-374. (Review of ghrelin/GHS in cancer; GH/IGF-1 can stimulate growth of some tumors (theoretical concern); GHSR-1a expressed in some tumors (testicular, ovarian, prostate, breast, GI); hexarelin/GHS may have direct effects on tumor cells (some studies show anti-proliferative/apoptotic effects, others show proliferative effects — context-dependent); active malignancy generally considered contraindication for GHS/GH therapy; cancer survivors with GH deficiency may sometimes be treated after careful evaluation; provides balanced view of cancer considerations for hexarelin use)
10. World Anti-Doping Agency (WADA). Peptide hormones, growth factors, and related substances — hexarelin and other GHS on the prohibited list. WADA Prohibited List. 2026. (WADA prohibited list; hexarelin classified as peptide hormone / growth hormone secretagogue; banned in-competition and out-of-competition for athletes; GH-releasing and performance-enhancing potential (increased lean mass, fat loss, recovery); other prohibited GHS include GHRP-2, GHRP-6, ipamorelin, anamorelin, ibutamoren/MK-677; testing methods: urine/blood mass spectrometry for hexarelin and metabolites; athletes should not use hexarelin; provides regulatory context for hexarelin as banned performance-enhancing substance)