Current Medicinal Chemistry - Volume 11, Issue 1, 2004

Cardiac arrhythmias represent a major area of cardivascular disease research. Of the possible medical treatments of arrhythmias, drug therapy has gained great importance. In spite of the significant progress achieved in the basic understanding of the electrophysiology and molecular biology of transmembrane ion channels and transporters underlying the mechanism of cardiac arrhythmias and possible drug actions, d Read More

One possible mechanism of action of the available K-channel blocking agents used to treat arrhythmias is to selectively inhibit the HERG + MIRP channels, which carry the rapid delayed rectifier outward potassium current (IKr). These antiarrhythmics, like sotalol, dofetilide and ibutilide, have been classified as Class III antiarrhythmics. However, in addition to their beneficial effect, they substantially lengthen ventricular repolari Read More

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial cardiovascular morbidity and mortality. The arrhythmia can be initiated and / or maintained by rapidly firing foci, single- and multiple-circuit reentry. Once initiated, AF alters atrial electrical and structural properties (atrial remodeling) in a way that promotes its own maintenance and recurrence and may alter the re Read More

The slowly (IKs) and rapidly (IKr) activating delayed rectifier K+ currents play important roles in cardiac ventricular repolarization. Compared with IKr, however, IKs has important distinguishing characteristics, including ß-adrenergic receptor stimulation and accumulation at rapid rates that may impart significant therapeutic relevance. Therefore, development of selective IKs inhibitors has been pursued as a strategy for providing Read More

The goal of this paper is two fold. First, we attempt to review the reports available on the role of IKs in myocardial repolarization. Based on theoretical considerations and experimental results, it seems reasonable to assume that IKs blockade will lengthen the action potential. However, results obtained with IKs blockers, like chromanol 293B or L-735,821, are conflicting, since from slight lengthening to marked prolongati Read More

Cardiac arrhythmias represent a major area of cardiovascular research, and for drug therapy, a large choice of antiarrhythmic agents have been available. However, clinical trials with antiarrhythmic drugs have recently indicated that serious side effects may considerably limit the use of various antiarrhythmic agents, in particular, for preventing arrhythmia-related mortality. Amiodarone with its complex mode of action, w Read More

A major goal in contemporary drug design is to develop new ligands with high affinity of binding toward a given protein receptor. Pharmacophore, which is the three-dimensional arrangement of essential features that enable a molecule to exert a particular biological effect, is a very useful model for achieving this goal. If the three-dimensional structure of the receptor is known, pharmacophore is a complementary tool to st Read More

This article reviews the docking field starting from basic docking algorithms and describing the latest advances. We present the algorithmic framework and classify the state of-the-art methods. We point out the bottlenecks of the methods, like flexibility, absence of absolute scoring functions and explain what types of information can potentially be added to improve the results.