Linzess MOA (Mechanism of action) is different from most other medications used to treat constipation and IBS (Irritable Bowel Syndrome) such as Miralax.
Linzess (Linaclotide) is the first-in-class medicine that acts on the intestinal epithelial cells and stimulates the transmembrane Guanylate Cyclase 2C receptors (GC-2C).
Activation of guanylate cyclase 2 C receptors results in the activation of cyclic GMP inside the cells as well as outside the cells. This results in the opening of the cystic fibrosis transmembrane conductance regulator (CFTR) channels which allows the flow of electrolyte-rich fluid into the intestinal lumen [Ref].
Linzess MOA in relieving Constipation:
Linzess causes the secretion of chloride and bicarbonate-rich fluid into the intestinal lumen. This increases the water content of the food and hence softens the stools.
In addition, Linaclotide activates the intestinal smooth muscles to propel the food forward. This in turn initiates peristaltic movements pushing the food forward.
Thus, unlike most laxatives, Linzess has a dual mechanism of action in relieving chronic constipation. It adds fluid to the food and increases gut peristaltic movements reducing the transit time.
Linzess has not been studied for gastroparesis but because it increases intestinal motility, Linzess may need to be studied in individuals with gastroparesis.
Linzess MOA in relieving abdominal pain:
The activation of extracellular cGMP by Linzess is said to inhibit the pain receptors present in the intestinal mucosa. Thus, Linaclotide blocks the visceral pain pathways associated with chronic constipation, abdominal spasms, and IBS.
In animal models, Linzess has been seen to have direct effects on the pain receptors present in the brain. However, the likely mechanism of pain relief is because of the direct inhibition of pain pathways arising from the intestinal smooth muscles. and epithelial cells.
Other less-known mechanisms of Linzess:
Linzess does not affect the dopamine and serotonin levels in the brain. However, because most individuals with IBS have associated anxiety, it was observed that individuals in the Linzess group had improvement in their anxiety scores compared to placebo medicines.
This justifies the role of Linzess in individuals with IBS-C as it relieves constipation and simultaneously relieves anxiety associated with IBS.
Linzess relieves constipation, and visceral pain, and may improve anxiety associated with chronic constipation and IBS.