Amiloride (hydrochloride) (hydrate) (Synonyms: MK-870)

Amiloride is a potassium-sparing diuretic.^1,2 It is an inhibitor of the epithelial sodium channel (ENaC; K_0.5 = 2.6 µM for recombinant δENaC expressed in X. laevis oocytes).³ It inhibits sodium transport from bovine kidney cortex membrane vesicles with an IC₅₀ value of 0.4 µM.⁴ Amiloride inhibits the urokinase-type plasminogen activator (u-PA; K_i = 7 µM) and cardiac Na⁺/H⁺-ATPase (IC₅₀ = 83.8 µM).^5,6 It also inhibits calcium currents mediated by transient receptor potential polycystin 3 (TRPP3; IC₅₀ = 143 µM).⁷ Amiloride (30 mg/kg) reduces mean arterial pressure in spontaneously hypertensive, but not normotensive, rats.⁸ Formulations containing amiloride have been used alone, and in combination with thiazide diuretics, in the treatment of hypertension.

1.Lingueglia, E., Voilley, N., Lazdunski, M., et al.Physiological society symposium: Ion channels in health and disease. Molecular biology of the amiloride-sensitive epithelial Na+ channelExp. Physiol.81483-492(1996) 2.Qadri, Y.J., Rooj, A.K., and Fuller, C.M.ENaCs and ASICs as therapeutic targetsAm. J. Physiol. Cell Physiol.302(7)C943-C965(2012) 3.Waldmann, R., Champigny, G., Bassilana, F., et al.Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channelJ. Biol. Chem.270(46)27411-27414(1995) 4.Kleyman, T.R., Yulo, T., Ashbaugh, C., et al.Photoaffinity labeling of the epithelial sodium channelJ. Biol. Chem.261(6)2839-2843(1986) 5.Vassalli, J.D., and Belin, D.Amiloride selectively inhibits the urokinase-type plasminogen activatorFEBS Lett.214(1)187-191(1987) 6.Kleyman, T.R., and Cragoe, E.J., Jr.Amiloride and its analogs as tools in the study of ion transportJ. Membr. Biol.105(1)1-21(1988) 7.Dai, X.Q., Ramji, A., Liu, Y., et al.Inhibition of TRPP3 channel by amiloride and analogsMol. Pharmacol.72(6)1576-1585(2007) 8.Barrett, R.J., and Kau, S.T.Myocardial and vascular actions of amiloride in spontaneously hypertensive ratsJ. Pharmacol. Exp. Ther.239(2)365-374(1986)