Potential-dependent inhibition of cardiac Ca2+ inward currents by Ro 40-5967 and verapamil: relation to negative inotropy.

Eur J Pharmacol

Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Published: April 1991

Ro 40-5967 is a structurally novel Ca2+ channel blocker which binds to the [3H]desmethoxyverapamil receptor in cardiac membranes with a potency similar to that of verapamil but which has considerably fewer negative inotropic effects. In the present study, the inward Ca2+ current was measured in isolated myocytes with the whole-cell patch-clamp technique. It was found that at a physiological membrane potential (-80 mV) Ro 40-5967 was also less potent than verapamil in inhibiting this current, and that negative inotropy and Ca2+ channel blockade were correlated.

Download full-text PDF

Source
http://dx.doi.org/10.1016/0014-2999(91)90430-xDOI Listing

Publication Analysis

Top Keywords

negative inotropy
8
ca2+ channel
8
potential-dependent inhibition
4
inhibition cardiac
4
ca2+
4
cardiac ca2+
4
ca2+ currents
4
currents 40-5967
4
40-5967 verapamil
4
verapamil relation
4

Similar Publications

The ex vivo effects of hypoxanthine-tricyclano, a synthetic adenosine analogue, on rat left and right atria.

Gen Physiol Biophys

November 2024

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Hypoxanthine-tricyclano is a synthetic adenosine analogue, in which adenine and ribose have been replaced by hypoxanthine and a morpholino-derived tricyclic moiety, respectively. We investigated whether hypoxanthine-tricyclano could influence atrial inotropy and/or chronotropy, two important functions regulated by the A1 receptor, the main adenosine receptor type of the supraventricular myocardium. Paced left atria and spontaneously beating right atria, isolated from male, 30-35 weeks old, Wistar rats, were used.

View Article and Find Full Text PDF

Structure-activity optimization of ryanodine receptor modulators for the treatment of catecholaminergic polymorphic ventricular tachycardia.

Heart Rhythm

October 2024

Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas; Department of Integrative Physiology, Baylor College of Medicine, Houston, Texas; Department of Neuroscience, Baylor College of Medicine, Houston, Texas; Division of Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Division of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Space Medicine, Baylor College of Medicine, Houston, Texas. Electronic address:

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia disorder associated with lethal arrhythmias. Most CPVT cases are caused by inherited variants in the gene encoding ryanodine receptor type 2 (RYR2).

Objective: The goal of this study was to investigate the structure-activity relationship of tetracaine derivatives and to test a lead compound in a mouse model of CPVT.

View Article and Find Full Text PDF

The developmental changes in the excitation-contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in the guinea pig it decreases during the fetal stage but turns into an increase just before birth. Such changes can be attributed to changes in the repolarizing potassium currents.

View Article and Find Full Text PDF

Quinoline-related antimalarial drugs have been associated with cardiotoxicity risk, in particular QT prolongation and QRS complex widening. In collaboration with Medicines for Malaria Venture, we discovered novel plasmepsin X (PMX) inhibitors for malaria treatment. The first lead compounds tested in anesthetized guinea pigs (GPs) induced profound QRS widening, although exhibiting weak inhibition of NaV1.

View Article and Find Full Text PDF

Persistent sinus tachycardia (pST) has been associated with adverse cardiovascular events in critically ill patients. Pharmacological control of heart rate with negative inotropic agents has proven to be safe but could be potentially dangerous in patients with concomitant right ventricular (RV) dysfunction. Ivabradine, a medication devoid of negative inotropy, could be a potentially safe solution for this patient population when adequate heart rate control is desired.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!