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Bepridil is a dihydropyridine that has anti-anginal and anti-arrhythmic actions by blocking calcium channels in heart and smooth muscle.1,2 It is recognized as a non-selective channel blocker, altering myocardial Ca2+, Na+, and K+ currents.3 For example, it blocks voltage-gated Ca2+ (Cav3.2) and K+ (hERG and KCNQ4) channels, sarcoplasmic ATP-sensitive K+ (KATP) channels, and Na+-activated (KNa) channels (IC50s = 7.1, 22, 9.4, 10, and 2.2 µM, respectively).4,5,6,2 It also activates mitochondrial ATP-sensitive KATP channels (ED50 = 27.5 µM).7
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1. The mechanism of action of calcium antagonists relative to their clinical applications. Br. J. Clin. Pharmacol. 21(Suppl 2), 109S-121S (1986).
2. Molecular pharmacology of human Cav3.2 T-
3. Effect of bepridil in atrial fibrillation inducibility facilitated by vagal nerve stimulation. Prevention of vagal nerve activation-
4. Predicting hERG activities of compounds from their 3D structures: Development and evaluation of a global descriptors based QSAR model. Eur. J. Med. Chem. 46(2), 618-630 (2011).
5. KCNQ4 channels expressed in mammalian cells: Functional characteristics and pharmacology. Am. J. Physiol. Cell Physiol. 280(4), C859-C866 (2001).
6. Bepridil blunts the shortening of action potential duration caused by metabolic inhibition via blockade of ATP-
7. Bepridil, an antiarrhythmic drug, opens mitochondrial KATP channels, blocks sarcolemmal KATP channels, and confers cardioprotection. J. Pharmacol. Exp. Ther. 316(1), 182-188 (2006).