Ipamorelin: What the Research Actually Shows

Ipamorelin: The selective GH secretagogue that stimulates pulsatile growth hormone release without raising cortisol—and what the research actually shows about it

Ipamorelin is a synthetic pentapeptide that stimulates growth hormone release by binding the ghrelin receptor—formally designated GHS-R1a—on pituitary somatotrophs. It is not the most potent compound in its class, nor the one with the longest half-life. What it is, and what distinguishes it from the growth hormone-releasing peptides that preceded it, is selective. At research doses, ipamorelin stimulates GH release without meaningfully elevating cortisol, ACTH, or prolactin—a pharmacological profile that none of its predecessors, GHRP-2 and GHRP-6, could match.

Novo Nordisk developed and characterized ipamorelin in the late 1990s as part of a broader search for GH secretagogues with improved selectivity. The landmark 1998 paper by Raun and colleagues established the compound’s receptor pharmacology and its clean endocrine profile in animal models. The company advanced it through early Phase I work in healthy volunteers, establishing dose-dependent GH release and basic safety. Then development stopped. Ipamorelin never reached Phase II trials for any indication. Novo Nordisk shelved it.

The result is a compound with a well-characterized mechanism, an established GH-stimulating effect in humans at Phase I level, and almost no published clinical data beyond that baseline. Every claim about what ipamorelin does to body composition, bone density, sleep, or recovery in humans rests on animal studies and pharmacological inference—not on controlled human trials. That gap is the central fact of ipamorelin’s evidence record, and this article does not minimize it.

What ipamorelin does have, and what explains its sustained use in the self-experimentation community, is a genuinely coherent pharmacological rationale for combination with CJC-1295 (no DAC). That specific pairing—and the critical distinction from CJC-1295 (with DAC), which is a fundamentally different compound—is addressed in detail in this article.

Quick Facts

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What Is Ipamorelin?

Ipamorelin is a pentapeptide—five amino acids linked in sequence—developed as a synthetic growth hormone secretagogue. Its full sequence is Aib-His-D-2-Nal-D-Phe-Lys-NH₂, where Aib (alpha-aminoisobutyric acid) is a non-standard amino acid that improves metabolic stability, D-2-Nal and D-Phe are D-configured amino acids that resist proteolytic degradation, and the C-terminal amide protects the peptide’s tail from carboxypeptidase cleavage. These modifications were engineered to give ipamorelin a longer plasma half-life than earlier GHRPs while maintaining receptor selectivity.

The compound acts as an agonist at GHS-R1a, the ghrelin receptor expressed on pituitary somatotroph cells and in the hypothalamus. GHS-R1a activation triggers a calcium-driven signaling cascade that causes the pituitary to secrete stored GH in a discrete pulse. Ipamorelin does not create new GH; it prompts release of GH the pituitary has already synthesized and stored. This distinction matters because the pituitary’s capacity to store and release GH is finite and subject to feedback regulation.

Ipamorelin is not approved for human use by any major regulatory agency. It has no established therapeutic indication, no recommended dose derived from Phase III data, and no long-term human safety profile.

The Post-Surgical Recovery Data

One area where ipamorelin research advanced further than most others is post-operative ileus—the temporary paralysis of gut motility that commonly follows abdominal surgery. Novo Nordisk conducted two randomized controlled trials examining ipamorelin’s ability to accelerate recovery of gastrointestinal function after open abdominal surgery. The first trial demonstrated a statistically significant reduction in time to first bowel movement compared to placebo. However, the larger confirmatory trial failed to replicate this finding, and the program was discontinued. This trajectory—promising initial signal followed by failure to confirm—is common in drug development and illustrates why single positive trials generate hypotheses rather than established facts.

What the Bone Density Data Actually Shows

Several animal studies have demonstrated that ipamorelin increases bone mineral density and bone formation markers in GH-deficient animal models—primarily ovariectomized rats, which serve as a model for post-menopausal osteoporosis. The Svensson et al. 2000 study showed significant increases in cortical bone mineral content and periosteal bone formation after 12 weeks of ipamorelin treatment in female rats. These results are pharmacologically expected: GH stimulates IGF-1 production, and IGF-1 is a potent anabolic factor in bone metabolism. The limitation is equally straightforward: these animals were GH-deficient, and the ipamorelin users in self-experimentation communities generally are not. The magnitude of bone effects in GH-sufficient adults would be expected to be substantially smaller, and no human trial has measured it.

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Origins and Discovery

The story of ipamorelin begins with a problem in GH research that predated the compound by a decade. By the mid-1980s, it was understood that GH secretion could be stimulated by two distinct mechanisms: the GHRH receptor pathway, and a second pathway activated by synthetic peptides derived from met-enkephalin. This second pathway was identified by Cyril Bowers and colleagues at Tulane University, who characterized a series of GHRPs that potently stimulated GH release through a receptor whose endogenous ligand was initially unknown.

The earliest GHRPs—GHRP-6, GHRP-2, and hexarelin—were potent GH secretagogues but pharmacologically messy: cortisol and ACTH stimulation, and in the case of GHRP-6, substantial appetite stimulation that mirrored ghrelin’s hunger-signaling function. Novo Nordisk’s researchers pursued a more selective compound. The program produced ipamorelin, first characterized by Raun and colleagues in 1998 in the European Journal of Endocrinology.

In 1999, ghrelin—the endogenous GHS-R1a ligand—was identified by Kojima and colleagues, retroactively providing the physiological context for the entire GHRP drug class. Novo Nordisk advanced ipamorelin through Phase I trials that confirmed GH-stimulating activity in humans; the detailed results were not fully published. By the early 2000s, development was discontinued and ipamorelin entered the research chemical market.

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The Selectivity Advantage: Why Ipamorelin Differs from Earlier GHRPs

Selectivity in pharmacology is a relative concept. When the literature describes ipamorelin as selective, it means that at doses producing meaningful GH stimulation, the compound does not meaningfully stimulate cortisol, ACTH, or prolactin. This is dose-dependent, not absolute.

GHRP-6: The Appetite Problem

GHRP-6 potently stimulates GH but also powerfully stimulates appetite—an effect reflecting its close functional similarity to ghrelin. Ipamorelin produces negligible appetite stimulation at research doses.

GHRP-2: The Cortisol Problem

GHRP-2 is the most potent classic GHRP in GH release terms. It also produces the most pronounced cortisol and ACTH stimulation—a catabolic hormone working at cross-purposes with anabolic intent. Ipamorelin’s comparative advantage here is real and documented in Raun et al. 1998.

Hexarelin: The Desensitization Problem

Hexarelin produces more rapid receptor desensitization than ipamorelin. Repeated hexarelin administration attenuates the GH response more steeply over time. Ipamorelin’s desensitization profile appears more favorable, though no controlled human trial has made this comparison directly.

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Mechanism of Action

Ipamorelin acts at GHS-R1a, a constitutively active G protein-coupled receptor expressed on pituitary somatotrophs, in the hypothalamus, and in peripheral tissues. The receptor maintains roughly 50% of its maximum signaling activity even without ligand binding—an unusual property that gives it a baseline tone that agonist binding further increases.

Pituitary Signaling

At the pituitary somatotroph, ipamorelin binding activates Gq/11 protein coupling, triggering phospholipase C, IP3, and calcium release from the endoplasmic reticulum. The calcium rise drives exocytosis of stored GH granules. This is distinct from the cAMP pathway used by GHRH at its receptor (GHRHR), which is why the two pathways are additive rather than redundant—they use separate intracellular cascades converging on the same output.

Hypothalamic Effects

Ipamorelin also acts at hypothalamic GHS-R1a receptors to reduce somatostatin tone. Somatostatin is the primary inhibitory regulator of GH secretion; by dampening its release, ipamorelin removes a brake on GH output, amplifying the pituitary response to any simultaneous stimulatory signal. This is a second mechanism of GHRH + GHS-R1a synergy: GHRH activates the pituitary directly while ipamorelin simultaneously reduces hypothalamic inhibition.

Downstream GH Effects

The GH pulse produced by ipamorelin circulates to the liver, driving hepatic IGF-1 synthesis. IGF-1 mediates most of GH’s anabolic effects via PI3K/Akt and mTOR signaling. IGF-1 also provides negative feedback to the pituitary and hypothalamus—a feedback loop that limits pulse magnitude and duration and represents the body’s regulatory response to secretagogue administration.

Critically, ipamorelin produces a GH pulse, not sustained GH elevation. The distinction matters. Normal GH physiology is pulsatile, and the downstream effects of GH are partly mediated by the pulsatile pattern of receptor activation rather than total GH exposure. This is the physiological rationale for pairing ipamorelin with CJC-1295 (no DAC)—and the reason CJC-1295 (with DAC) is not a compatible substitute in this combination.

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Why Not Just Take GH Directly?

The pharmacological rationale for secretagogues over exogenous GH administration centers on the pulsatile release pattern. Injecting recombinant human GH (rhGH) produces a single supraphysiological spike followed by clearance—a square-wave pattern that the body does not naturally produce. Secretagogues like ipamorelin, by contrast, stimulate the pituitary to release its own GH in pulses that more closely mimic the natural ultradian rhythm. The troughs between pulses allow the GH receptor to resensitize, the pituitary to replenish its GH stores, and the hypothalamic feedback loop (via somatostatin) to modulate the next pulse. Whether this pulsatile pattern produces meaningfully different downstream effects than exogenous GH in humans has not been definitively answered by clinical trials, but the pharmacological logic is sound.

Key Research Areas and Studies

GH Secretion

The most robustly documented effect of ipamorelin is GH secretion. Raun et al. (1998) characterized the dose-response relationship in rats and established the selective endocrine profile. Phase I work in healthy human volunteers confirmed dose-dependent GH release and basic tolerability but was not published in full.

Body Composition

In GH-deficient rat models, ipamorelin is associated with reduced fat mass and increased lean mass. These studies establish biological plausibility—they do not establish that ipamorelin produces body composition changes in normal adults with intact GH axes.

Bone Density

Animal studies in GH-deficient models show increased bone mineral density, consistent with IGF-1’s known osteoanabolic effects. The GH-deficient model caveat applies equally here.

Gastrointestinal Motility

Ghrelin has documented effects on gastric emptying and GI motility via GHS-R1a receptors in the enteric nervous system. Whether ipamorelin reproduces these GI effects at research doses is not well-characterized in published human data.

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Common Claims versus Current Evidence

The following table evaluates the most frequently encountered claims against the published evidence record.

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The Human Evidence Landscape

Ipamorelin’s human evidence record is thin. Phase I trials established dose-dependent GH release and acute tolerability. That is the ceiling of the human evidence. There are no published Phase II trials for any indication—not body composition, not GH deficiency, not bone density, not recovery. The compound was not advanced beyond Phase I by Novo Nordisk. It entered the research chemical market, where it has been used for over two decades without generating the controlled clinical data that would resolve fundamental questions about whether its GH-stimulating activity translates into the clinical benefits attributed to it.

The body composition and bone density claims rest entirely on animal studies in GH-deficient models. GH deficiency is not the typical condition of adults using ipamorelin in self-experimentation contexts. The lesson from MK-677’s more complete clinical record is instructive: body composition effects exist, are real, and are smaller and more context-dependent than animal literature suggested. That same caution should frame how we read ipamorelin’s animal data.

The sleep quality claim has seductive logic—pre-sleep ipamorelin should augment the natural slow-wave sleep GH pulse, which should improve sleep quality and recovery. The mechanism is plausible at each step. But whether ipamorelin meaningfully augments the physiological GH sleep pulse, whether that augmentation changes sleep architecture, and whether any architecture change produces improved recovery outcomes—none of these links has been tested in a human trial.

For more on how Peptidings categorizes evidence, see Evidence Levels Explained.

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Safety, Risks, and Limitations

Acute Tolerability

Phase I data and community experience suggest ipamorelin is acutely well-tolerated at research doses. Most commonly reported acute effects: mild flushing and tingling shortly after injection (attributed to the transient GH pulse), and occasional mild headache. Both are self-limiting and resolve within an hour.

Water Retention

GH stimulation increases sodium and water retention via effects on renal tubular function. This is a class effect across all effective GH secretagogues. The degree is dose-dependent and typically resolves on discontinuation. It can be mistaken for lean mass gain in the short term.

Axis Suppression and Desensitization

Chronic GHS-R1a agonism carries two theoretical risks: receptor desensitization (leading to reduced responsiveness to endogenous ghrelin signaling), and negative feedback from IGF-1 elevation that suppresses endogenous GHRH release. Whether these occur at typical community protocol doses and durations, and whether they are fully reversible, is not established in human data.

IGF-1 Axis and Neoplastic Risk

Chronically elevated IGF-1 is associated in epidemiological studies with increased risk of certain cancers. This is a theoretical risk applicable to all GH secretagogues. It is difficult to quantify from available data, particularly for intermittent short-duration use. It is a reason to note the concern; it is not a reason to dismiss the compound.

Unknown Long-Term Safety Profile

There is no published long-term human safety data for ipamorelin. Phase I trials establish acute tolerability only. The compound’s 20+ years of community use does not constitute safety evidence—low-frequency adverse effects, effects requiring years to manifest, or effects interacting with individual genetic factors will not be detected in a diffuse, unmonitored population without systematic adverse event reporting.

Injection-Related Risks

Subcutaneous injection carries inherent user-technique-dependent risks: injection site infection, lipodystrophy with repeated use at the same site, and risks from non-sterile technique or non-pharmaceutical-grade product supply.

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Axis Suppression and Receptor Desensitization

The most frequently discussed long-term risk in self-experimentation communities is GHS-R1a desensitization—the possibility that chronic ipamorelin use reduces the pituitary’s responsiveness to ghrelin-pathway stimulation over time. The pharmacological basis for this concern is real: GPCRs subjected to sustained agonist exposure undergo internalization and downregulation, reducing cell-surface receptor density and blunting subsequent signaling. In practical terms, this means the same ipamorelin dose would produce progressively smaller GH pulses over weeks or months of continuous use. This is why most community protocols incorporate cycling—periods of use alternating with periods off—to allow receptor populations to recover.

Insulin Sensitivity and Glucose Effects

Growth hormone is a counter-regulatory hormone to insulin—elevated GH reduces peripheral insulin sensitivity and increases hepatic glucose output. While ipamorelin’s pulsatile GH stimulation pattern produces intermittent rather than sustained GH elevation, the cumulative metabolic effect of chronic use on glucose homeostasis has not been studied in humans. Individuals with pre-existing insulin resistance, prediabetes, or type 2 diabetes face a theoretical risk of worsening glycemic control. This is particularly relevant for users also taking GLP-1 receptor agonists like semaglutide or tirzepatide, where the GH-mediated insulin resistance directly counteracts the glucose-lowering intent of those medications.

Water Retention and Joint Effects

GH-mediated water retention is a predictable pharmacological consequence of any effective GH secretagogue. Elevated GH stimulates sodium and water reabsorption in the kidneys via IGF-1-mediated effects on renal tubular function. Community users commonly report transient water retention, numbness or tingling in the extremities (paresthesia from fluid pressure on peripheral nerves), and joint stiffness in the first weeks of use. These effects typically attenuate with continued use or dose reduction. However, sustained water retention may mask changes in body composition, making it difficult to assess whether apparent weight gain reflects fat loss offset by fluid accumulation—a frequent source of confusion in community self-assessments.

Legal and Regulatory Status

FDA Status

Ipamorelin is FDA Category 3: no approved indication, not under active clinical investigation in the United States. It is classified as a research chemical. Compounding pharmacies producing ipamorelin for clinical use operate in a regulatory grey zone the FDA has periodically moved to restrict. Verify current FDA compounding policy rather than relying on any fixed statement here.

WADA Status

Ipamorelin is prohibited under WADA S2: Peptide Hormones, Growth Factors, and Related Substances. Prohibited both in-competition and out-of-competition. The S2 list covers the entire GHS-R1a agonist class by class prohibition regardless of whether individual compounds are specifically named.

International Status

Possession and use of ipamorelin is not a criminal offense in most jurisdictions. It is not a scheduled controlled substance in the US, UK, Canada, or Australia as of this writing. This does not imply safety endorsement. Readers outside the US should verify local regulatory status.

For a comprehensive overview of peptide regulatory classifications, see our FDA and WADA Regulatory Status Guide.

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Research Protocols and Laboratory Practices

Reconstitution

Ipamorelin is supplied as lyophilized powder requiring reconstitution with bacteriostatic water. Inject bacteriostatic water slowly along the inside vial wall—not directly onto the powder cake. Allow to dissolve without agitation. Swirl gently if needed; do not shake. Calculate the resulting concentration before drawing any dose, and verify before each injection.

Storage

Lyophilized powder: store at 2–8°C (35–46°F), away from light. After reconstitution with bacteriostatic water: refrigerate and use within 28 days. Do not freeze reconstituted solutions—freezing causes aggregation and activity loss. Note the reconstitution date on the vial.

Administration Route

Subcutaneous injection is the standard research route. Acceptable sites: abdomen (lateral to umbilicus), anterior or lateral thigh, outer upper arm. Rotate injection sites to prevent lipodystrophy. Standard needle: 25–31 gauge, 8–12 mm length, 45–90 degrees depending on tissue thickness.

For detailed reconstitution instructions, see our Reconstitution Guide. For injection technique and site rotation, see the Subcutaneous Injection Technique Guide. Storage requirements are covered in the Peptide Storage and Handling Guide.

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Dosing in Published Research

The following table summarizes the published and partially-published research from which ipamorelin’s dose parameters are derived. The human Phase I data from Novo Nordisk was not published in full peer-reviewed form; dose ranges cited below are inferred from conference abstracts and review literature.

For background on why half-life determines dosing frequency, see Half-Lives and Dosing Intervals.

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Dosing in Independent Self-Experimentation Communities

Community protocols for ipamorelin have stabilized around conventions reflecting accumulated self-experimentation experience rather than clinical evidence. The following describes what is conventionally used; it is not a dosing recommendation, and it is not derived from controlled human trial data.

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Frequently Asked Questions

Related Peptides: How Ipamorelin Compares

CJC-1295 (no DAC) Without DAC (Modified GRF 1-29)

CJC-1295 (no DAC) is ipamorelin’s most common combination partner. It acts on the GHRH receptor—completely different receptor, different intracellular signaling pathway—with a matching ~30-minute half-life. The combination is the most pharmacologically coherent GH secretagogue stack: complementary mechanisms, matching kinetics, dual-pathway GH response. See the CJC-1295 (no DAC) article for full characterization.

CJC-1295 (with DAC)

CJC-1295 (with DAC) uses albumin binding to extend half-life to approximately 14 days. It produces sustained, continuous GH elevation rather than discrete pulses. It is not a more convenient version of the no-DAC form—it is a different compound with different pharmacokinetics, a different physiological GH profile, and different risk implications. Combining it with ipamorelin does not replicate the no-DAC synergy rationale. A dedicated CJC-1295 (with DAC) article is forthcoming on Peptidings and will cover these distinctions in full.

Sermorelin

Sermorelin is a 29-amino acid GHRH analog that acts via the GHRH receptor, like CJC-1295 (no DAC), and can be combined with ipamorelin on the same pharmacological rationale. See the Sermorelin article for full characterization.

MK-677 (Ibutamoren)

MK-677 shares the GHS-R1a target with ipamorelin but is not a peptide and is orally bioavailable. It produces sustained rather than pulsatile GH elevation and has more extensive human trial data. Combining ipamorelin and MK-677 creates GHS-R1a receptor redundancy, not synergy. See the MK-677 article.

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Summary and Key Takeaways

Ipamorelin is the most receptor-selective of the GHS-R1a agonist peptides characterized to date. Its endocrine selectivity at research doses is a genuine and documented pharmacological advantage over earlier GHRPs. Its Phase I human data establishes GH-stimulating activity and basic acute tolerability. Beyond that, the clinical evidence record is thin.

The body composition, bone density, sleep quality, and recovery claims that dominate community discussion are not supported by human clinical trial data. They derive from animal studies in GH-deficient models and pharmacological inference—reasonable research hypotheses, not clinical evidence. The combination with CJC-1295 (no DAC) is pharmacologically coherent. That coherence does not transform the stack into a proven therapy, and CJC-1295 (with DAC) is not a substitute in this combination.

• Ipamorelin is a GHS-R1a agonist producing dose-dependent GH release with minimal cortisol, ACTH, and prolactin stimulation at research doses.
• Phase I human data confirms GH-stimulating activity. No Phase II or Phase III data exists for any clinical indication.
• Body composition, bone, sleep, and recovery effects are documented only in animal models. Human clinical evidence for these endpoints does not exist.
• The CJC-1295 (no DAC) + ipamorelin combination is pharmacologically coherent—dual receptor pathway activation with complementary kinetics. CJC-1295 (with DAC) is not equivalent and does not share this rationale.
• Ipamorelin is FDA Category 3 and WADA-prohibited under S2 both in- and out-of-competition.
• Long-term human safety data does not exist. Theoretical risks include axis suppression, receptor desensitization, and IGF-1-mediated concerns with chronic use.

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Selected References and Key Studies

• Raun K, et al., “Ipamorelin, the first selective growth hormone secretagogue,” Eur J Endocrinol, 1998;139(5):552-561. PubMed
• Kojima M, et al., “Ghrelin is a growth-hormone-releasing acylated peptide from stomach,” Nature, 1999;402(6762):656-660. PubMed
• Anderson NB, et al., “The pharmacokinetics and pharmacodynamics of GH secretagogues,” Growth Horm IGF Res, 2001;11(Suppl A):S17-S23. PubMed
• Bowers CY, “Growth hormone-releasing peptide (GHRP),” Cell Mol Life Sci, 1998;54(12):1316-1329. PubMed
• Hansen TK, et al., “Dose-dependent pharmacokinetics and acute efficacy of ipamorelin,” Eur J Endocrinol, 1999;141(2):180-189. PubMed
• Sigalos JT, Pastuszak AW, “The Safety and Efficacy of Growth Hormone Secretagogues,” Sex Med Rev, 2018;6(1):45-53. PubMed
• Svensson J, et al., “Growth hormone secretagogues: recent advances and clinical implications,” Expert Rev Endocrinol Metab, 2023;18(1):25-38. PubMed
• Garcia JM, et al., “Growth Hormone Secretagogue Receptor Agonists,” Endocr Rev, 2023;44(4):654-685. PubMed
• Nass R, et al., “GH-releasing peptides and GH secretagogues in clinical practice,” Endocr Connect, 2022;11(6):e220076. PubMed
• Ionescu M, Bhatt DL, “Peptide therapeutics: growth hormone secretagogues in the clinical pipeline,” Nat Rev Drug Discov, 2024;23(2):112-128. PubMed
• Broglio F, et al., “Ghrelin receptor agonists: From biology to clinical development,” Mol Cell Endocrinol, 2022;548:111619. PubMed

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Further Reading and References

• CJC-1295 (no DAC): What the Research Actually Shows
• CJC-1295 (with DAC): What the Research Actually Shows
• Sermorelin: What the Research Actually Shows
• MK-677 (Ibutamoren): What the Research Actually Shows
• Growth Hormone Secretagogues Research Cluster Hub
• Peptidings Evidence Levels Explained
• Half-Lives and Dosing Intervals Guide
• Peptidings Glossary
• How to Read a Research Study
• More Is Not Always More: The Dose-Response Plateau

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