Bepridil hydrochloride is a long-acting calcium channel blocker. Bepridil hydrochloride blocks Ca²⁺, Na⁺, and K⁺ channels and inhibits calmodulin. Bepridil hydrochloride can be used in research related to chronic stable angina and arrhythmias[1-4].
In vitro, Bepridil hydrochloride (25-50μM) was used to treat A2058, A375, and C8161 melanoma cells preloaded with Fluo-4 AM (5μM) for 40 minutes. Bepridil hydrochloride significantly increased cytoplasmic Ca²⁺ signal levels; Bepridil hydrochloride (10-50μM) was used to treat A2058 melanoma cells for 18-24 hours, causing G0/G1 phase cell cycle arrest and enhanced apoptosis[5]. Bepridil hydrochloride (0.78–200μM) was used to treat Vero E6 or A549/ACE2 cells infected with SARS-CoV-2 (MOI=0.5) for 3 days and A549/ACE2 cells for 4 days. Bepridil hydrochloride prevented virus-induced cytopathic effects and inhibited viral replication[6].
In vivo, Bepridil hydrochloride (5mg/kg/day) was intraperitoneally injected into NSG mice intravenously transplanted with CLL cells for 20 days. Bepridil hydrochloride significantly reduced the percentage of leukemic cell infiltration in the spleen by enhancing apoptosis and decreasing NOTCH1 activation[7]. Bepridil hydrochloride (12mg/kg) was intraperitoneally injected once or twice daily into BALB/c mice infected with Marburg virus (195PFU) for 10 days. Bepridil hydrochloride significantly increased the survival rate of infected mice[8].
References:
[1] Pang DC, Sperelakis N. Inhibitory action of bepridil (CERM-1978) on calcium binding to cardiac sarcolemma of guinea pig. Biochem Pharmacol. 1981 Aug 15;30(16):2356-8.
[2] Mras S, Sperelakis N. Bepridil (CERM-1978) an verapamil depression of contractions of rabbit aortic rings. Blood Vessels. 1981;18(4-5):196-205.
[3] Mras S, Sperelakis N. Bepridil (CERM-1978) blockade of action potentials in cultured rat aortic smooth muscle cells. Eur J Pharmacol. 1981 Apr 24;71(1):13-9.
[4] Flaim SF, Stranieri MT, Mathiasen JR. Effects of bepridil hydrochloride on cardiocirculatory dynamics, coronary vascular resistance, and cardiac output distribution in normal, conscious rats. J Cardiovasc Pharmacol. 1988 Mar;11(3):363-72.
[5] Liu Z, Cheng Q, Ma X, et al. Suppressing Effect of Na+/Ca2+ Exchanger (NCX) Inhibitors on the Growth of Melanoma Cells. Int J Mol Sci. 2022 Jan 14;23(2):901.
[6] Vatansever EC, Yang KS, Drelich AK, et al. Bepridil is potent against SARS-CoV-2 in vitro. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2012201118.
[7] Baldoni S, Del Papa B, Dorillo E, et al. Bepridil exhibits anti-leukemic activity associated with NOTCH1 pathway inhibition in chronic lymphocytic leukemia. Int J Cancer. 2018 Aug 15;143(4):958-970.
[8] DeWald LE, Dyall J, Sword JM, et al. The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease. J Infect Dis. 2018 Nov 22;218(suppl_5):S588-S591.