Phenamil (methanesulfonate)

Phenamil is an inhibitor of transient receptor potential polycystin-L (TRPP3; IC₅₀ = 140 nM) and a derivative of amiloride (Item No. 14409).¹ It also inhibits the epithelial sodium channel (ENaC; IC₅₀ = 400 nM).² Phenamil decreases basal short-circuit currents in human and ovine bronchial epithelial cells with IC₅₀ values of 75 and 116 nM, respectively.³ It inhibits potassium chloride-induced contractions in isolated rat endothelium-denuded aortic rings (EC₅₀ = 6.76 µM) and increases contractile force in isolated rat right ventricular papillary muscles (EC₅₀ = 16.98 µM).⁴ Phenamil (15 and 30 mg/kg per day) reduces pulmonary artery medial wall thickness and decreases right ventricular peak pressure in a rat model of chronic hypoxia-induced pulmonary hypertension.⁵

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1. Dai, X.Q., Ramji, A., Liu, Y., et al. Inhibition of TRPP3 channel by amiloride and analogs. Mol. Pharmacol. 72(6), 1576-1585 (2007).

2. Hirsh, A.J., Molino, B.F., Zhang, J., et al. Design, synthesis, and structure - activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: Drugs for cystic fibrosis and chronic bronchitis. J. Med. Chem. 49(14), 4098-4115 (2006).

3. Hirsh, S.J., Sabater, J.R., Zamurs, A., et al. Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease. J. Pharmacol. Exp. Ther. 311(3), 929-938 (2004).

4. Brown, L., Cragoe, E.J., Jr., Abel, K.C., et al. Amiloride analogues induce responses in isolated rat cardiovascular tissues by inhibition of Na⁺/Ca²⁺ exchange. Naunyn Schmiedebergs Arch Pharmacol. 344(2), 220-224 (1991).

5. Chan, M.C., Weisman, A.S., Kang, H., et al. The amiloride derivative phenamil attenuates pulmonary vascular remodeling by activating NFAT and the bone morphogenetic protein signaling pathway. Mol. Cell. Biol. 31(3), 517-530 (2011).