Research information only. PrecisePep is an educational library. It is not medical advice and is not intended to assist, encourage or enable self-administration. The compounds documented here are research chemicals — most are not approved for human use. Read the full disclaimer.
PrecisePep/Peptide Library/Linaclotide
Gastrointestinal & Mucosal
Linzess® · Constella® · MD-1100 · GC-C agonist
A 14-residue peptide that is swallowed rather than injected, is not meant to be absorbed, and works entirely on the luminal surface of the gut it passes through. The only orally administered peptide drug in this library.
Almost every peptide in this library has the same problem: swallow it and it is destroyed. That is why the rest of this site is about injections, and why the reconstitution guide exists at all. Linaclotide is the exception, and it solves the problem by not needing to survive for very long or go anywhere in particular.
It is a 14-amino-acid peptide locked into a rigid shape by three disulphide bonds — a structure borrowed from the heat-stable enterotoxins that certain strains of E. coli use to cause travellers' diarrhoea. Those toxins work by activating guanylate cyclase-C on the intestinal surface, driving chloride and bicarbonate into the lumen and pulling water with them. Linaclotide does the same thing on purpose, at a dose calibrated to relieve constipation rather than to cause disease.
Because it acts on the outside of the epithelium and is barely absorbed, its systemic pharmacology is close to non-existent — a rare situation where "poor bioavailability" is the design specification rather than the obstacle.[1] It also reduces visceral pain in IBS through a separate downstream effect on afferent nerves, which is why it outperforms an ordinary laxative in that condition.
Linaclotide is a prescription medicine and this page publishes no unsupervised dosing for it. It is here because the conditions index covers IBS, and because it is a useful corrective: a peptide drug for gut symptoms that is taken as a capsule, is approved, works by a fully characterised mechanism, and has none of the sterility or supply problems that dominate every other gut-directed compound discussed on this site.
GC-C agonism on the luminal surface. Guanylate cyclase-C is expressed on the apical membrane of intestinal epithelial cells. Its natural ligands are guanylin and uroguanylin. Activation raises intracellular cyclic GMP.
CFTR-mediated secretion. Cyclic GMP activates protein kinase G II, which phosphorylates the cystic fibrosis transmembrane conductance regulator. Chloride and bicarbonate move into the lumen; water follows osmotically. Stool softens and transit accelerates.
Visceral analgesia — the part that distinguishes it from a laxative. Cyclic GMP also exits the cell basolaterally and acts on submucosal afferent nerve endings, reducing their firing in response to distension. In animal models this reduces visceral hypersensitivity independently of the secretory effect, which is the mechanistic account for the pain benefit in IBS.[1]
Why the paediatric contraindication exists. GC-C expression is higher in the immature intestine. In neonatal mice, linaclotide produced fluid secretion severe enough to cause death from dehydration within twenty-four hours. It is contraindicated below two years of age, and there is insufficient information on GC-C expression in that age group to characterise the risk in humans.[2]
Effects that have been reported. A study-tier entry means a result was published — not that the effect is established, reproducible, or transferable from a rodent to a person.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Randomised placebo-controlled trials in adults with irritable bowel syndrome with constipation reported improvement in a composite endpoint combining complete spontaneous bowel movements and abdominal pain — pain and bowel function together, not either alone.
Separate randomised trials support a distinct approval in chronic idiopathic constipation, at a different dose from the IBS-C indication.
IBS-C from seven years and functional constipation from two years, following paediatric randomised trials — an unusually broad paediatric licence for a peptide.
Plasma concentrations are generally below the limit of quantification at therapeutic doses. The drug is degraded in the intestinal lumen and largely recovered in faeces, which is why it has essentially no systemic drug interactions.
The visceral analgesic mechanism is supported by preclinical work and is the reason it is positioned as an IBS drug rather than as a constipation drug with an IBS indication attached.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
The afferent-nerve mechanism has prompted interest in other visceral pain states. It remains a preclinical and early-clinical proposition.
Mechanistically plausible, and not the indication it is approved for — peripherally acting mu-opioid receptor antagonists occupy that space with direct evidence.
The disulphide-locked structure is the reason this molecule can be swallowed. It is cited as a design precedent, though the lesson generalises poorly: it works because it does not need to be absorbed.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Patient reporting frequently describes an effect within the first day or two, and the most common complaint is that the first few doses overshoot.
The label specifies at least 30 minutes before the first meal of the day. Taking it with food is widely reported to increase looser stools, which matches the label.
The recurring comparison in patient discussion is against osmotic laxatives, which move stool without touching the pain component.
An inexpensive oral prescription capsule with no systemic effect has nothing to offer the research-chemical market, and it does not appear there.
Adverse effects, contraindications and unknowns. The grey-market tier is where under-reporting is worst: uncontrolled use produces no systematic safety surveillance at all, so absence of a reported harm is not evidence of safety.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
In neonatal mice, linaclotide caused deaths from dehydration within twenty-four hours through age-dependent elevated GC-C agonism. This is the most serious item on the label and it is a hard contraindication, not a caution.
The most common adverse reaction and the most common reason for discontinuation, typically starting within the first two weeks. Severe diarrhoea warrants stopping and clinical assessment.
Increasing intestinal secretion proximal to an obstruction is not a survivable idea.
The other common adverse events across the programme, generally mild.
The downstream consequence of the primary effect, and the reason paediatric use is monitored closely.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
With negligible systemic absorption there is little basis for pharmacokinetic interaction — an unusual and genuine advantage rather than an absence of data.
Symptoms return on discontinuation. It manages a chronic condition rather than resolving it.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Consistently the dominant early complaint.
Patients frequently describe moving to a lower capsule strength, which is what the multiple strengths exist for.
Reported, and contrary to the label, which specifies before the first meal of the day.
Figures below are documented, not recommended. Study ranges come from published protocols in the stated model; grey-market ranges are what the research community reports using and carry no safety validation of any kind.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
One capsule daily at least 30 minutes before the first meal of the day. Capsules are swallowed whole; the label provides alternative administration for those who cannot swallow capsules.
A lower dose range than the IBS-C indication, with the 72 mcg strength available where the higher dose is not tolerated.
Functional constipation from 2 years and IBS-C from 7 years use distinct age- and indication-specific doses defined in the label.
| Indication | Dose | Population | Note |
|---|---|---|---|
| IBS-C | 290 mcg once daily | Adults | ≥30 min before first meal |
| IBS-C | Age-specific dose | Children 7+ | See label |
| Chronic idiopathic constipation | 145 mcg once daily | Adults | 72 mcg where 145 not tolerated |
| Functional constipation | Age-specific dose | Children 2+ | See label |
| Under 2 years | Contraindicated | — | Fatal dehydration in neonatal mice |
| Obstruction | Contraindicated | — | Known or suspected mechanical |
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
A common clinical approach given how consistently diarrhoea is the limiting factor. Reasoning, not a labelled titration — the drug is not formally titrated.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
It is a prescription capsule at a fixed strength, used as prescribed. There is no reconstitution, no vial, and no calculator entry.
Combination effects. Almost no peptide combination has been studied as a combination in humans; stack logic is overwhelmingly mechanistic inference and community practice. Each linked compound has its own page.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Negligible absorption means negligible interaction potential — the practical advantage of a drug that never enters the circulation.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Both increase luminal water. Combining them typically produces diarrhoea rather than better control.
A structured low-FODMAP trial with reintroduction, soluble fibre and gut-directed psychological therapy have evidence bases of their own that this drug is added to, not a substitute for.
Those act — if at all — on mucosal repair and inflammation. Linaclotide acts on secretion and afferent signalling. Same organ, unrelated mechanisms, and only one of them has randomised human evidence.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
The common pattern in patient reporting, and the sensible one.
Whole schedules — dosing, titration, cycle length, and off-time — as documented in trials, as proposed from mechanism, and as circulated in the research community. Reproduced for study and comparison only.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Twelve- and twenty-six-week randomised placebo-controlled trials using FDA composite responder endpoints requiring simultaneous improvement in abdominal pain and complete spontaneous bowel movements.
Once daily, at least 30 minutes before the first meal, on an empty stomach — deviation from which predictably increases diarrhoea.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Coeliac disease and inflammatory bowel disease should be excluded before an IBS label is accepted and treated. This is more important than the choice of drug.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
The practical routine most patients converge on, and it matches the label.
The approved indications are covered above. What makes this compound worth a conditions section in a library of injectables is the design lesson: it is swallowed, and it works, because it never needs to be absorbed.
Approved for IBS with constipation and chronic idiopathic constipation, with paediatric indications. Contraindicated under two years of age — a hard contraindication derived from deaths due to dehydration in neonatal mice — and in known or suspected mechanical gastrointestinal obstruction.
Pathophysiology
Not a condition. The reason almost every other compound in this library is injected.
Mechanistic rationale
Peptides are destroyed in the gut, which is why this site has a reconstitution guide at all. Linaclotide gets around that with a 14-residue structure locked by three disulphide bonds and a target on the luminal surface of the epithelium. It does not need to survive absorption because it does not need to be absorbed. The lesson generalises poorly — it works precisely because its target is on the outside — but it is worth knowing that oral peptide drugs are possible when the target cooperates.
Community reports
Not a grey-market compound. Nothing in this market has anything to gain from an inexpensive oral prescription capsule with no systemic effect.
Components carrying the argument: Disulphide-locked structure, luminal target
Pathophysiology
Visceral hypersensitivity amplifies pain from normal gut distension and is central to IBS.
Mechanistic rationale
Cyclic GMP produced in the epithelium exits basolaterally and reduces firing of submucosal afferent nerves, which is a genuinely separate mechanism from the secretory effect and is why this outperforms an osmotic laxative on pain. That has prompted interest in other visceral pain states, which remains preclinical and early clinical.
Community reports
Patients consistently describe the pain benefit as the distinguishing feature versus laxatives they tried first.
Components carrying the argument: cGMP → afferent nerve firing
Pathophysiology
Opioids act on enteric mu receptors to slow transit, and the constipation does not attenuate with tolerance the way analgesia does.
Mechanistic rationale
Mechanistically plausible and not the indication it holds. Peripherally acting mu-opioid receptor antagonists were developed specifically for this and address the cause rather than the consequence.
Community reports
Used off-label in this setting.
Components carrying the argument: Secretory and prokinetic effect
| Question | Position |
|---|---|
| Route | Oral capsule — the only one in this library |
| Why that works | Target is on the luminal surface; absorption not required |
| Systemic exposure | Negligible — hence no meaningful drug interactions |
| Distinguishing effect | Visceral pain, via a separate cGMP mechanism |
| Under 2 years | Contraindicated |
| Grey market | None — nothing to gain |
For IBS: a structured low-FODMAP trial with reintroduction, soluble fibre, and gut-directed cognitive behavioural therapy or hypnotherapy, which has better evidence than most drug options. Excluding coeliac disease and inflammatory bowel disease before accepting an IBS label matters more than the choice of treatment. For constipation: fibre, fluid, osmotic laxatives, and the secretagogues and prokinetics where those fail.
Physical-chemistry reference for laboratory handling of the lyophilised material. Reproduced so that stability and concentration mathematics can be studied — see the calculator for the arithmetic and the reconstitution guide for sterile technique.
None — it is an oral capsule. This is the only compound in this library that requires no injection, no reconstitution and no sterile technique, and the only one for which the calculator has nothing to contribute.
Store in the original bottle at controlled room temperature. Keep the desiccant in the bottle and keep the bottle tightly closed — the capsules are moisture-sensitive. Do not subdivide or repackage into pill organisers.
Not applicable. Supplied as 72, 145 and 290 mcg capsules.
Moisture is the failure mode. The desiccant is not packaging filler; removing it or transferring capsules to another container degrades the product.
Regulatory status changes and differs by country. This is a summary for orientation, not legal advice — check your own jurisdiction.
Approved prescription medicine. Licensed as Linzess in the United States and Constella in Europe for irritable bowel syndrome with constipation and for chronic idiopathic constipation, with paediatric indications from two years for functional constipation and seven years for IBS-C.
Contraindicated in children under two years of age. This is derived from deaths due to dehydration in neonatal mice and is a hard contraindication. It is also contraindicated in known or suspected mechanical gastrointestinal obstruction.
Plecanatide (Trulance) is a closely related guanylate cyclase-C agonist based on uroguanylin rather than the heat-stable enterotoxin scaffold, approved for the same indications and carrying the same paediatric contraindication.
Regulatory and trial claims re-checked against primary sources on 16 August 2026. Checked: paediatric contraindication under 2 years; current label. Approvals, trial readouts and compounding decisions move faster than anything else on this page — a date here means someone looked, not that nothing has changed since.
Not a performance compound and not addressed as such under the WADA Prohibited List. Verify against the current list if competing.
Links resolve to PubMed records, trial registries, publisher pages or primary documents. Where a body of work rather than a single paper is cited, the link opens a PubMed query so the full result set — including newer papers than this page — can be reviewed. Verify every claim against the primary source before relying on it.
For educational and research reference only. Nothing on this site is medical advice, a recommendation, or an instruction to administer any substance to a human being. Every figure on this page is a record of what has been reported, not a recommendation. Full disclaimer.
