Plecanatide
An approved oral peptide for chronic constipation and IBS-C, designed to mimic uroguanylin and act preferentially in the acidic upper intestine.
Gut & Digestive
Linaclotide
An approved oral peptide for IBS with constipation and chronic idiopathic constipation. It acts entirely inside the gut and is essentially not absorbed.
Overview
Linaclotide binds a receptor on the surface of the intestinal lining and triggers fluid secretion into the bowel, which softens stool and speeds transit. It also appears to reduce pain signalling from the gut — the same second messenger it raises inside the cell leaks out and quietens the nerve endings sitting just outside. It stays in the intestine, so it does not produce systemic effects.
A 14-amino-acid peptide with three disulfide bonds, structurally related to bacterial heat-stable enterotoxins and to the endogenous ligands guanylin and uroguanylin. Agonises guanylate cyclase-C on the luminal surface of intestinal epithelium, raising intracellular cGMP, which activates CFTR and drives chloride and bicarbonate secretion with obligate water. Extracellular cGMP efflux is proposed to reduce afferent nociceptor firing, explaining the visceral pain benefit in IBS-C. Systemic absorption is negligible at therapeutic doses.
Research areas
IBS with constipationChronic constipationVisceral pain
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| 290 mcg orally once daily on an empty stomach for IBS with constipation | Approved product labelling |
| 145 mcg once daily for chronic idiopathic constipation, with 72 mcg available for tolerability | Approved product labelling |
Trial status
Multiple completed phase 3 trials in both indications.
Reported safety signals
- Diarrhoea is the most common adverse effect and the leading cause of discontinuation.
- Contraindicated in patients under 2 years old — fatal dehydration occurred in juvenile mice, and this is a boxed warning.
- Contraindicated with known or suspected mechanical gastrointestinal obstruction.
- Severe diarrhoea can cause electrolyte disturbance, particularly in older adults.
Common questions
Is linaclotide absorbed into the bloodstream?
Essentially not at therapeutic doses. It acts on receptors facing into the gut lumen and is degraded there. That is why it has no meaningful systemic side effect profile — everything it does, and everything that goes wrong with it, happens in the intestine.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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