Tenapanor (AZD1722) HCl is a potent, orally active sodium/hydrogen exchanger isoform 3 (NHE3) inhibitor. Tenapanor HCl reduces intestinal phosphate absorption predominantly through the reduction of passive paracellular phosphate flux. Tenapanor HCl has the potential to be used in research on hyperphosphatemia.
Tenapanor hydrochloride is a minimally absorbed small molecule sodium/hydrogen exchange isomer 3 (NHE3) inhibitor. NHE3 is involved in the uptake of sodium ions and water into the intestinal lumen, and by inhibiting NHE3, tenapanor is expected to reduce sodium absorption and increase fecal sodium and fluid excretion.
Tenapanor hydrochloride is generally well tolerated, with diarrhea being the most common adverse reaction. Diarrhea is usually transient (lasting 1 week) and mild to moderate in severity. Diarrhea develops within a week of starting treatment in approximately half of cases and within the first 3 weeks of treatment in two-thirds of cases. Other possible side effects include abdominal pain, nausea, bloating, and flatulence[1].
Synthesis of Tenapanor hydrochloride
Tenapanor hydrochloride (0.15, 0.5 mg/kg; p.o.) reduces passive paracellular phosphate absorption in rats[1].
Tenapanor hydrochloride (0.15 mg/kg; p.o.; twice-daily for 11 consecutive days) increases the reduction in urinary phosphorus excretion in rats[2].
| Animal Model: | Rats (intestinal loop model)[1] |
| Dosage: | 0.15, 0.5 mg/kg |
| Administration: | P.o. |
| Result: | Reduced passive paracellular phosphate absorption by reduced urinary phosphate and sodium excretion after the high-phosphate meal and increased sodium and phosphate delivery to the cecum. |
| Animal Model: | 8 weeks, 250 g male Sprague–Dawley rats[2] |
| Dosage: | 0.15 mg/kg in combination with sevelamer (0%, 0.75%, 1.5%, and 3% (wt/wt)) |
| Administration: | Oral gavage; twice-daily for 11 consecutive days |
| Result: | Significantly augmented the reduction in urinary phosphorus excretion. |
[1] WILLIAM D CHEY. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2).[J]. American Journal of Gastroenterology, 2021, 116 6: 1294-1303. DOI:10.14309/ajg.0000000000001056.
