Capromorelin
Also known as: CP-424391, capromorelin tartrate, GHSR agonist, oral ghrelin mimetic
Non-peptide growth hormone secretagogue (GHS); selective ghrelin receptor (GHSR-1a) agonist; orexigenic agent; oral small-molecule G-protein-coupled receptor ag
What it is
Capromorelin is a prescription oral ghrelin-receptor agonist used to stimulate appetite and reverse weight loss in dogs and cats with chronic illness. Athletes and researchers have studied it for growth hormone release, lean-mass preservation, and age-related muscle decline. Its oral bioavailability and clean safety profile distinguish it from injectable alternatives.
The scientific side
capromorelin is a non-peptide small molecule that acts as a selective, potent agonist at the growth hormone secretagogue receptor type 1a (GHSR-1a; also called GHS-R1a), a constitutively active Gq-protein-coupled receptor expressed highly in the hypothalamus, pituitary gland, and numerous peripheral tissues including the gastrointestinal tract and autonomic ganglia. Capromorelin mimics the endogenous ligand ghrelin by binding to GHSR-1a and triggering downstream phospholipase C activation, intracellular inositol trisphosphate generation, and calcium mobilization. At the pituitary, this results in pulsatile growth hormone (GH) release that is partially dependent on endogenous growth hormone-releasing hormone (GHRH); the magnitude of the GH pulse is greatest with infrequent dosing and attenuates over days of repeated administration due to receptor desensitization, a phenomenon demonstrated in both canine and human studies (PMID 27597271; PMID 19174493). Despite pulsatile GH attenuation, downstream insulin-like growth factor-1 (IGF-1) concentrations remain sustainably elevated during multi-week treatment courses, which is thought to mediate the anabolic and body-composition effects including lean mass accretion and weight gain (PMID 27597271; PMID 19174493). In the hypothalamus, GHSR-1a stimulation activates neuropeptide Y/agouti-related peptide orexigenic circuits in the arcuate nucleus, producing robust appetite stimulation and increased caloric intake—the primary mechanism underlying capromorelin's approved veterinary indications. In the gastrointestinal tract, capromorelin stimulates GHSR-1a receptors on enteric cholinergic neurons to accelerate gastric emptying of solids in an atropine-sensitive, nitric oxide-dependent manner equipotent to native ghrelin and the peptide agonist GHRP-6. In the autonomic nervous system, capromorelin activates GHSR-1a on lumbosacral preganglionic neurons, stimulating propulsive colorectal contractions and bladder contractile activity through spinal autonomic circuits—mechanisms distinct from its hypothalamic appetite effects and potentially relevant to neurogenic bowel and bladder dysfunction (PMID 21625243; PMID 20497419). Cardiovascular effects including transient blood pressure decreases have been observed with capromorelin at high doses, attributed to activation of a novel non-GHSR-1a vascular receptor rather than the canonical ghrelin receptor. Cortisol and IGF-1 also rise acutely after each dose but return to baseline within hours, consistent with indirect hypothalamic-pituitary-adrenal axis stimulation secondary to GH release. Transient glucose elevations warrant monitoring in diabetic patients.
Class: Non-peptide growth hormone secretagogue (GHS); selective ghrelin receptor (GHSR-1a) agonist; orexigenic agent; oral small-molecule G-protein-coupled receptor agonist
Administration & storage
- Administration
- Oral solution administration (licensed veterinary route; approved for dogs and cats)Intravenous administration used in research settings only (pharmacology and cardiovascular studies in rats and dogs; not a clinical route)Intraspinal injection used in preclinical autonomic studies only (not a clinical route)
- Storage
- Licensed veterinary oral solutions (ENTYCE, Elura) should be stored as per manufacturer labeling, generally at controlled room temperature (15–30°C) and protected from light. Shake well before use. Discard unused portions according to labeling. For compounded preparations, storage conditions depend on formulation and should be specified by the compounding pharmacy.
- Cautions
- NOT approved for human use; no human dose has been established by a regulatory authority.,WADA-prohibited substance: use by competitive athletes constitutes an anti-doping rule violation; athletes and support staff handling veterinary preparations risk inadvertent positive tests via oral ingestion or dermal absorption.,Transient hyperglycemia: capromorelin transiently elevates fasting blood glucose and blunts first-phase insulin secretion in cats and dogs; use with caution in diabetic animals and monitor glucose closely (PMID: 32619812; PMID: 35689953).,Gastrointestinal adverse effects: emesis, hypersalivation, diarrhea, and loose stools are the most commonly reported adverse events at approved and supra-therapeutic doses in dogs and cats.,IGF-1 elevation: sustained IGF-1 increases during prolonged therapy may have unknown long-term implications for neoplastic growth; theoretical concern in patients with active malignancy.,Cortisol and adrenal axis stimulation: acute cortisol elevation post-dose occurs as a secondary pharmacodynamic effect; clinical significance in patients with adrenal or endocrine disorders is unclear.,Potential cardiovascular effects at high doses: capromorelin at pharmacological doses caused transient blood pressure decreases in anesthetized rats via a novel non-GHSR-1a receptor mechanism; clinical relevance at approved doses is not established.,Species-specific efficacy: capromorelin did not significantly affect food intake or fecal output in healthy rabbits at 3 mg/kg and did not mitigate opioid-associated weight loss in guinea pigs at 5 mg/kg, highlighting that effects are not universal across species.
Legal & regulatory status
Capromorelin oral solution (ENTYCE, 30 mg/mL) received FDA approval in May 2016 for stimulation of appetite in dogs (Canis lupus familiaris), followed by commercial launch in autumn 2017 (PMID: 37493940; PMID:…
Capromorelin is explicitly prohibited in sports under the WADA Prohibited List within category S2 — Peptide Hormones, Growth Factors, Related Substances and Mimetics — because it stimulates endogenous growth hormone…
Capromorelin has not received a Notice of Compliance (NOC) or veterinary drug authorization from Health Canada for any human or veterinary indication as of the knowledge cutoff. Veterinary use of US-approved…
What it's studied for
- Appetite stimulation and weight gain in dogs with inappetence Pivotal RCT (veterinary, FDA registration-grade)
- Weight loss management in cats with chronic kidney disease (CKD) Pivotal RCT (veterinary, FDA registration-grade)
- Lean mass preservation and physical function improvement in older adults with functional decline Human RCT (Phase II/III, terminated early per pre-specified criteria)
- Neurogenic bowel dysfunction — stimulation of defecation in spinal cord injury Animal (proof-of-principle, rat)
- Gastroprokinetic effect — acceleration of gastric emptying Animal (in vivo and in vitro, mouse)
- Cancer-associated anorexia and cachexia — veterinary appetite restoration Veterinary clinical review / FDA-approved off-label use discussion
- IGF-1 elevation and potential Alzheimer's disease Abeta clearance (negative finding) Animal (translational, dogs and mice)
- Growth hormone derivative development platform — medicinal chemistry lead optimization Preclinical (in vitro / animal)
Safety signals
- Transient hyperglycemia and impaired glucose tolerance
- Emesis and hypersalivation
- Elevated blood lipids and alkaline phosphatase
- Prolonged PR interval on electrocardiogram
- Insulin resistance and small increases in HbA1c in elderly humans
- Transient blood pressure decrease at high doses (preclinical cardiovascular signal)
- Risk of inadvertent anti-doping rule violation from veterinary product exposure
- Species-dependent lack of efficacy (non-responsive species)
All studies (13)
Frequently asked
Is capromorelin legal for humans to use?
Capromorelin is not approved by the FDA, Health Canada, or any known major regulatory authority for use in humans. It is approved only as a veterinary drug for appetite stimulation in dogs (ENTYCE) and weight loss management in cats with chronic kidney disease (Elura). Using veterinary capromorelin in humans would be unapproved and unregulated. Additionally, capromorelin is listed on the WADA Prohibited List under S2 (Growth Hormone Secretagogues), meaning competitive athletes who use it — even inadvertently — may face anti-doping sanctions.
Has capromorelin been tested in human clinical trials?
Yes. A Phase II/III randomized, double-masked, placebo-controlled multicenter trial enrolled 395 men and women aged 65–84 years to evaluate capromorelin's effects on body composition and physical function over up to 12 months. All active dosing arms produced sustained IGF-1 elevation, lean mass gains (~1.4 kg at 6 months), and modest improvements in physical performance tests (tandem walk, stair climb). However, adverse effects including fatigue, insomnia, and small metabolic changes (elevated glucose and HbA1c) were also observed. The trial was terminated early per pre-specified criteria, and capromorelin was never submitted for human FDA approval.
Does capromorelin increase growth hormone levels?
Yes, capromorelin stimulates pulsatile growth hormone (GH) release by acting on the GHSR-1a receptor in the pituitary and hypothalamus. In dogs, a single oral dose acutely elevated GH, which returned to baseline by 8 hours post-dose. With repeated daily dosing, the GH response attenuates (desensitization), but IGF-1 — the downstream anabolic mediator — remains sustainably elevated throughout multi-week treatment (PMID 27597271; PMID 19174493). Because of this GH/IGF-1-stimulating activity, capromorelin is classified as a prohibited growth hormone secretagogue under WADA anti-doping rules.
What are the risks of using veterinary capromorelin in humans?
No veterinary formulation has been tested for safety or efficacy in humans at appropriate doses, and the excipients in veterinary oral solutions are not formulated for human consumption. Known pharmacodynamic risks from the human and animal literature include transient hyperglycemia and impaired insulin sensitivity (relevant for people with diabetes or metabolic syndrome), cortisol elevation, potential for elevated blood lipids at higher doses, and possible blood pressure effects at supratherapeutic doses. Additionally, any competitive athlete using capromorelin faces a high risk of an anti-doping rule violation, as even small exposures produce detectable urine concentrations for up to 48 hours. Use in humans is not medically authorized and carries unquantified risk.
Can my pet's use of capromorelin cause me to fail a drug test?
Yes, this is a documented risk. A controlled study confirmed that oral ingestion of just 30 micrograms of capromorelin (equivalent to 1 microlitre of the Entyce product) produced detectable urine concentrations for up to 48 hours in adult human volunteers. Dermal absorption from handling the veterinary solution during pet administration (applying to an animal's mouth) also produced detectable urine levels. Athletes who administer capromorelin to their pets are at risk of an inadvertent adverse analytical finding under WADA anti-doping rules. Before 2022 no such positive test had been reported, but anti-doping authorities now have validated detection methods in place (PMID 37688359; PMID 33458843).
How does capromorelin differ from other growth hormone secretagogues like ibutamoren (MK-677)?
Capromorelin and ibutamoren (MK-677) are both non-peptide oral GHSR-1a agonists, but they differ structurally, pharmacokinetically, and in regulatory history. Capromorelin has received two FDA veterinary approvals (dogs and cats) and was studied in a large human aging trial, giving it the most rigorous regulatory evidence base of any oral GHS. Preclinical comparisons show capromorelin derivatives can be up to 100-fold more potent than ibutamoren at stimulating GH in rats. Neither compound is approved for human use. Both are prohibited by WADA. Neither has been approved for human use and their long-term safety in humans has not been fully established.