Walker, Michael J.A.

The chapter, "Targeting ischemic ventricular arrhythmias" was written by the listed authors including Leon J. Guppy (Douglas College Faculty). Methods in Pharmacology and Toxicology publishes cutting-edge techniques, including methods, protocols, and other hands-on guidance and context, in all areas of pharmacological and toxicological research. Each book in the series offers time-tested laboratory protocols and expert navigation necessary to aid toxicologists and pharmaceutical scientists in laboratory testing and beyond. With an emphasis on details and practicality, Methods in Pharmacology and Toxicology focuses on topics with wide-ranging implications on human health in order to provide investigators with highly useful compendiums of key strategies and approaches to successful research in their respective areas of study and practice. The revolution in molecular medicine makes it imperative to integrate the classical and molecular approaches to drug development for the treatment of heart disease, the number one killer in North America and Europe. In the Cardiac Drug Development Guide, basic medical researchers, clinicians, and pharmacologists join forces to comprehensively survey the most recent breakthroughs in molecular cardiology and review the latest drug discoveries in cardiac and cardiovascular medicine. Topics range from novel molecular targets for cardiac drug development, to functional endpoints for evaluating cardiac drug activity, to clinical aspects of cardiovascular therapeutics. The authors describe the most advanced procedures in cardiovascular pharmacology, including in vivo and in vitro whole animal studies, the electrophysiological methods used to study pacemaker cells, and the application of biochemical principles and technologies to novel therapeutic agents. Also discussed are the methods used to express the ion channels involved in cardiovascular pharmacology, adenoviral vector delivery for cardiovascular gene therapy, pharmacometrics in cardiovascular drug development, gender differences in heart failure, and angiogenesis therapies for coronary heart disease. Each chapter concisely illustrates the concepts described and includes comprehensive background information, detailed figures and tables, and an up-to-date list of the most important references. Comprehensive and easy-to-understand, the Cardiac Drug Development Guide offers pharmacologists, cardiologists, and physiologists not only a gold-standard survey of the many different methods being used to develop new heart drugs, but also details powerful new ways in which cardiovascular disease is targeted, from the whole organ to the genetic level. The purpose of this chapter is to ask why there has been so little success in developing new antiarrhythmic drugs and what can we do to increase our chances of success. Failure has been a fairly common theme in attempts to produce new antiarrhythmic drugs, particularly for lethal ventricular arrhythmias. The chapter considers old and new ways of finding novel drugs for lethal ventricular arrhythmias as a result of myocardial ischemia and infarction and describes new compounds selective for ischemia-induced ventricular tachycardia and fibrillation. --From publisher description.

It is our contention that functional pharmacology, particularly in vivo, must play a greater role in drug discovery if the promises of reductionist techniques are to be brought to full fruition. Despite the advent of high-throughput screening, combinatorial chemistry and informatics, the number of new chemical entities (NCEs) coming on the market has fallen. While the advent of these methodologies makes it possible to move very quickly from molecular target to lead compound, the problem of demonstrating therapeutic utility remains. Has proof of concept (in vivo) become the bottleneck in drug discovery? This article focuses on this problem, and discusses what can be done about it. [ABSTRACT FROM AUTHOR]