PHENAMIL METHANESULFONATE

TRPP3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a Ca ²⁺ -activated channel permeable to Ca ²⁺ , Na ⁺ , and K ⁺ . TRPP3 is implicated in regulation of pH-sensitive action potential in spinal cord neurons. Phenamil methanesulfonate (1 μM) decreases ⁴⁵ Ca ²⁺ uptake in a radiotracer uptake assay. It inhibits TRPP3-mediated Ca ²⁺ transport with an IC ₅₀ value of 0.28 μM in oocytes expressing TRPP3 or H2O-injected oocytes. Phenamil methanesulfonate is a more potent ENaC blocker than Amiloride, it inhibits the epithelial sodium channel (ENaC) with an IC ₅₀ of 400 nM (Amiloride=776 nM).Phenamil methanesulfonate inhibits basal short-circuit currents with IC ₅₀ values of 75 and 116 nM, respectively in both human and ovine bronchial epithelia cells.Phenamil methanesulfonate (0-20 μM; 14 days) elevates adipogenic gene expression, PPARγ, Fabp4, and lipoprotein lipase expression in a concentration-dependent manner ,and regulates adipogenesis in C3H10T1/2 cells.Phenamil methanesulfonate (0-20 μM; 7 or 14 days) modulates MC3T3-E1 osteoblastic differentiation, it increases Alkaline phosphatase (ALP) activity in MC3T3-E1 cells in a concentration-dependent manner.

Phenamil methanesulfonate (subcutaneous injection; 15 or 30 mg/kg; 21 days; infusion rate of 1 ml/h) reduces chronic-hypoxia-induced pulmonary artery hypertension (PAH). Additionally, the mRNA level of SMA, SM22, Id3, and Trb3 from the lung sample are also decreased by Phenamil under hypoxia or normoxia in rats. However, phenamil has little effect on pulmonary vasculature under physiological conditions.