Background: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat mode...

Background. Tachycardia enhances the channel-blocking effects of antiarrhythmic drugs. In contrast to the extensive data regarding the rate-dependent effects of sodium channel blockers in humans, little is known about the frequency-dependent effects of calcium channel blockers on human atrioventricular (AV) nodal properties. Accordingly, the purpose of this study was to evaluate the importance ...

BACKGROUND Diltiazem hydrochloride is a commonly prescribed benzothiazepine calcium channel blocker for the treatment of cardiovascular disease. Recently, 8 cases of diltiazem-induced photodistributed hyperpigmentation occurring predominantly in elderly African American women were reported. Here, we report occurrence for the first time in a light-skinned African American woman and a Hispanic wo...

Response to Sympathoinhibitory Effect of Diltiazem and Prevention of Aneurysm Formation We thank Dr Tsuda1 for the important remark and his interest in our work. Unfortunately, we did not perform measurements on the effect of diltiazem on sympathetic nerve activity in our study and as mechanism of action of the drug we observed some direct inhibitory action on the inflammatory activity of cultu...

To determine the effects of diltiazem, a new calcium antagonist, on myocardial ischemia, two experiments were performed. The results showed 1) the intravenous holus injection of large doses of diltiazem reduced ST segment elevation in open-chest dogs with acute coronary occlusion. The regional myocardial blood flow in the control area, as well as moderately and mildly ischemic areas increased s...

The goal of this study was to determine the effects of the L-type calcium channel blockers verapamil and diltiazem on the currents of voltage-gated potassium channel (fKv1.4ΔN), an N-terminal-deleted mutant of the ferret Kv1.4 potassium channel. Measurements were made using a two electrode voltage clamp technique with channels expressed stably in Xenopus oocytes. The fKv1.4ΔN currents displayed...

Kinetic parameters (k(inact) and K(I)) obtained in microsomes are often used to predict time-dependent inactivation. We previously reported that microsomal inactivation kinetic parameters of diltiazem underpredicted CYP3A inactivation in hepatocytes. In this study, we evaluated the contributions of inactivation and reversible inhibition of CYP3A by diltiazem and its N-desmethyl (MA) and N,N-did...

The purpose of this study was to determine if the known frequency-dependent effects of diltiazem on inward calcium current result in selective actions during supraventricular tachycardia. These effects were evaluated by use of an experimental model of orthodromic atrioventricular reentrant tachycardia (AVRT). AVRT was induced in 15 dogs over a wide range of retrograde conduction times before an...

Diltiazem is a calcium slow-channel blocking drug that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy 3 hours after a single oral dose of 120 mg, 12 men with chronic stable angina pectoris performed a maximal exercise test on a bicycle ergometer after ingesting either placebo or diltiazem administered in a double-blind fashion. During s...