Bepridil

Abstract

Bepridil is a calcium antagonist with direct negative chronotropic, dromotropic, inotropic and vasodilatory actions which reduces myocardial oxygen consumption and increases coronary blood flow, leading to a significant anti-ischaemic and antianginal effect in the absence of reflex tachycardia. In contrast to other calcium channel blockers, bepridil produces only modest peripheral vasodilatation and displays weak antihypertensive activity. Its plasma elimination half-life of 1 to 2 days permits once daily administration. Results of short term clinical trials have shown bepridil to be of comparable efficacy to nifedipine, verapamil, diltiazem, propranolol and nadolol in decreasing the frequency of anginal attacks and consumption of nitroglycerin (glyceryl trinitrate) in patients with stable angina. Bepridil is more effective than nifedipine in improving exercise performance in patients with stable angina. Although bepridil proved superior to diltiazem in improving exercise performance in patients refractory to diltiazem, further studies are required to confirm the efficacy of bepridil in patients refractory to, or intolerant of, other antianginal agents. Bepridil in therapeutic doses is well tolerated, and appears to have a similar adverse effect profile to the established calcium antagonists. However, rate-dependent prolongation of the QTc interval and development of torsade de pointes have been associated with the use of bepridil. Therefore, bepridil is contraindicated in patients with hypokalaemia, those receiving other drugs that may prolong the QT interval, and those with congenital QT interval prolongation. Future clinical research will help to further define the position of bepridil as an antianginal treatment relative to the traditional calcium antagonists; in the interim, bepridil is indicated for the treatment of patients with angina refractory to or intolerant of other agents.

Targeting Notch Trafficking and Processing in Cancers

“…The original GE-HTS screen also led to the identification of the FDA-approved ion flux Ca 2+ modulator, bepridil, a class IV antiarrhythmic drug [ 191 ] with limited toxic effects. This observation was leveraged to challenge a repurposing effort in NOTCH1 mutated cancers.…”

Antagonist molecules in the treatment of angina

“…Bepridil helps to decrease the frequency of angina attacks, as measured by the use of nitrates. However, concerns regarding prolongation of the corrected QT interval and torsade de pointes have limited its use in North America [45]. …”

“…As with the entire spectrum of coronary disease, optimal medical therapy and risk factor modification provides important prognostic and symptomatic benefit in these patients. A wide array of pharmacological armamentarium is now available to manage the patients with chronic stable angina as outlined in Table 1 [27, 31–36, 38–40, 42, 43, 45, 50, 51, 53, 54, 67, 72, 78, 80, 82–84, 87–92, 95, 97, 102, 107, 132–144]. …”

Suppression of Metastatic Ovarian Cancer Cells by Bepridil, a Calcium Channel Blocker

“…Bepridil is known as a calcium channel blocker, possessing a distinct electrophysiological profile [7,8]. It is widely utilized as a therapeutic agent for cardiovascular disorders, known for its ability to decrease myocardial oxygen consumption and enhance coronary blood flow [9]. The equilibrium column-binding technique revealed that bepridil exhibits specific binding affinity towards calmodulin-an intracellular calcium receptor protein-in Life 2023, 13, 1607 2 of 12 the presence of calcium ions.…”