Dolcanatide ia an orally administered analog of the human endogenous natriuretic hormone uroguanylin and guanylate cyclase C (GC-C) agonist, with potential laxative, anti-nociceptive and anti-inflammatory activities. Upon administration, dolcanatide, by mimicking uroguanylin, binds to and activates GC-C locally on endothelial cells in the gastrointestinal (GI) tract, without entering the systemic circulation. Activation of GC-C results in an increase in cyclic guanosine monophosphate (cGMP). Increased concentrations of cGMP lead to the activation of the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). CFTR activation increases the secretion of negatively charged ions, particularly chloride and bicarbonate, into the GI tract lumen, which further drives sodium ions and then water into the lumen. This leads to increased fluid secretion in the GI tract, accelerated transit and changes in stool consistency. In addition, ion channel modulation may decrease muscle contractions and the activity of pain-sensing nerves, thereby decreasing intestinal pain. Also, GC-C may inhibit the secretion of pro-inflammatory cytokines, which may ameliorate GI inflammation. Delconitide is in phase I clinical trial to study how well it works in preventing colorectal cancer in healthy participants.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models. | 2018-05-07 |
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| The Guanylate Cyclase C-cGMP Signaling Axis Opposes Intestinal Epithelial Injury and Neoplasia. | 2018 |
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| Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis. | 2015-11-06 |
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| Emerging treatments in Neurogastroenterology: Perspectives of guanylyl cyclase C agonists use in functional gastrointestinal disorders and inflammatory bowel diseases. | 2015-08 |
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| Pharmacology and clinical potential of guanylyl cyclase C agonists in the treatment of ulcerative colitis. | 2013 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT03300570
Single daily dose of 27 mg x 7 days
Route of Administration:
Oral
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