Tenapanor is an orally bioavailable inhibitor of sodium-hydrogen exchanger 3 (NHE-3; IC50 = 10 nM for the recombinant rat protein).1 Tenapanor (10 µM) inhibits intestinal fluid absorption in mouse jejunum, but not distal colon, in a closed intestine loop assay.2 It also lowers both the sodium and phosphate urinary-to-dietary ratio in a dose-dependent manner in rats.1 Tenapanor (5 mg/kg) reverses decreases in stool pellet numbers and water content induced by loperamide and prevents loperamide-induced constipation in mice.2 Formulations containing tenapanor have been used in the treatment of irritable bowel syndrome with constipation.
1.LabontÉ, E.D., Carreras, C.W., Leadbetter, M.R., et al.Gastrointestinal inhibition of sodium-hydrogen exchanger 3 reduces phosphorus absorption and protects against vascular calcification in CKDJ. Am. Soc. Nephrol.26(5)1138-1149(2015) 2.Haggie, P.M., Cil, O., Lee, S., et al.SLC26A3 inhibitor identified in small molecule screen blocks colonic fluid absorption and reduces constipationJCI Insight3(14)e121370(2018)