Linaclotide
Linaclotide is a medication people take for constipation and irritable bowel syndrome with constipation. It's a synthetic peptide—basically a tiny chain of amino acids, the building blocks of proteins—designed to mimic something your gut naturally encounters. Doctors prescribe it when people are struggling with chronic constipation or IBS-C because it actually works to get things moving and reduce the abdominal pain that often comes with it.
Here's how your body responds to it: when you take linaclotide, it travels to your intestines and finds specific receptors on the cells lining your gut—think of these as locks waiting for the right key. Linaclotide is that key. When it fits into these receptors, it triggers a cascade of signals inside your intestinal cells that tells them to release more water and electrolytes into your bowel. This extra fluid softens your stool and helps it move along faster, which is why you feel relief from constipation. But there's a bonus: that same signaling also has a painkilling effect on the nerves in your gut, reducing the cramping and discomfort you'd normally feel. The best part is that linaclotide stays put in your intestines and doesn't get absorbed into your bloodstream, so it only affects your gut without causing side effects elsewhere in your body.
Dosage Information
Typical Dose
72-290 mcg once daily (FDA-approved doses)
Frequency
Once daily on empty stomach 30 minutes before first meal
Administration
Oral capsule
Half-Life
~3 hours
Notes
FDA-approved for IBS-C (290 mcg) and chronic idiopathic constipation (72 mcg or 145 mcg). Must be taken on empty stomach. Keep away from children — dangerous if accidentally ingested.
Why this matters
Acts locally in the gut; minimal systemic absorption by design.
Protocol cycle
Where does Linaclotide sit?
See how this peptide compares across all 150 peptides in our database.
Evidence Score
0.80
Compound Data
Molecular Formula
C59H79N15O21S6
Molecular Weight
1526.80 g/mol
IUPAC Name
(2S)-2-[[(1R,4S,7S,13S,16R,21R,24R,27S,30S,33R,38R,44S)-21-amino-13-(2-amino-2-oxoethyl)-27-(2-carboxyethyl)-44-[(1R)-1-hydroxyethyl]-30-[(4-hydroxyphenyl)methyl]-4-methyl-3,6,12,15,22,25,28,31,40,43,46,51-dodecaoxo-18,19,35,36,48,49-hexathia-2,5,11,14,23,26,29,32,39,42,45,52-dodecazatetracyclo[22.22.4.216,33.07,11]dopentacontane-38-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic acid
PubChem CID
16158208Potential Side Effects
Linaclotide discussions
Quick Facts
- Administration
- Oral capsule
- Typical Dose
- 72-290 mcg once daily (FDA-approved doses)
- Frequency
- Once daily on empty stomach 30 minutes before first meal
- References
- 0 curated + 49 from PubMed
- Clinical Trials
- 50 registered
- Evidence Score
- 0.8 / 100
Frequently Asked Questions about Linaclotide
What is Linaclotide?
Linaclotide is a synthetic 14-amino-acid peptide agonist of guanylate cyclase-C (GC-C) receptors in the intestinal epithelium FDA-approved under the brand name Linzess for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. It represents one of the few gut peptides with full FDA approval and a robust clinical evidence base from multiple large Phase 3 trials. Linaclotide acts locally in the gut with minimal systemic absorption making it a highly targeted gastrointestinal therapeutic.
How does Linaclotide work?
Linaclotide mimics the heat-stable enterotoxins produced by E. coli binding to and activating guanylate cyclase-C receptors on intestinal epithelial cells. GC-C activation increases intracellular cGMP which activates CFTR chloride channels promoting chloride and bicarbonate secretion into the intestinal lumen. This osmotic effect increases luminal fluid content softening stool and accelerating intestinal transit. The elevated cGMP also has direct analgesic effects — it diffuses through the epithelium to afferent pain-sensing neurons reducing their sensitivity to colonic distension and explaining linaclotide's efficacy for abdominal pain in IBS-C beyond its laxative effects. Minimal systemic absorption means virtually no off-target effects.
What is the recommended dosage for Linaclotide?
The typical dose is 72-290 mcg once daily (FDA-approved doses). Once daily on empty stomach 30 minutes before first meal. Administration: Oral capsule. FDA-approved for IBS-C (290 mcg) and chronic idiopathic constipation (72 mcg or 145 mcg). Must be taken on empty stomach. Keep away from children — dangerous if accidentally ingested.
What are the side effects of Linaclotide?
Diarrhea (very common — most frequent reason for discontinuation). Abdominal pain (common). Flatulence (common). Serious dehydration with severe diarrhea (uncommon but important to monitor)
What is the Linaclotide cycle protocol?
Linaclotide is typically cycled continuous. Daily maintenance therapy, no cycling protocol
Questions reflect common community inquiries. This is not medical advice.