Voltage-Gated Ion Channels as Drug Targets


Book Description

Edited by the most prominent person in the field and top researchers at US pharmaceutical companies, this is a unique resource for drug developers and physiologists seeking a molecular-level understanding of ion channel pharmacology. After an introduction to the topic, the authors evaluate the structure and function of ion channels, as well as related drug interaction. A section on assay technologies is followed by a section each on calcium, sodium and potassium channels. Further chapters cover genetic and acquired channelopathies, before the book closes with a look at safety issues in ion channel drug development. For medicinal and pharmaceutical chemists, biochemists, molecular biologists and those working in the pharmaceutical industry.







Ion Channel Drug Discovery


Book Description

Ion channel drug discovery is a rapidly evolving field fuelled by recent, but significant, advances in our understanding of ion channel function combined with enabling technologies such as automated electrophysiology. The resurgent interest in this target class by both pharmaceutical and academic scientists was clearly highlighted by the over-subscribed RSC/BPS 'Ion Channels as Therapeutic Targets' symposium in February 2009. This book builds on the platform created by that meeting, covering themes including advances in screening technology, ion channel structure and modelling and up-to-date case histories of the discovery of modulators of a range of channels, both voltage-gated and non-voltage-gated channels. The editors have built an extensive network of contacts in the field through their first-hand scientific experience, collaborations and conference participation and the organisation of the meeting at Novartis, Horsham, increased the network enabling the editors to draw on the experience of eminent researchers in the field. Interest and investment in ion channel modulation in both industrial and academic settings continues to grow as new therapeutic opportunities are identified and realised for ion channel modulation. This book provides a reference text by covering a combination of recent advances in the field, from technological and medicinal chemistry perspectives, as well as providing an introduction to the new 'ion channel drug discoverer'. The book has contributions from highly respected academic researchers, industrial researchers at the cutting edge of drug discovery and experts in enabling technology. This combination provides a complete picture of the field of interest to a wide range of readers.




Structure, Function, and Modulation of Neuronal Voltage-Gated Ion Channels


Book Description

This book discusses voltage-gated ion channels and their importance in drug discovery and development. The book includes reviews of the channel genome, the physiological bases of targeting ion channels in disease, the unique technologies developed for ion channel drug discovery, and the increasingly important role of ion channel screening in cardiac risk assessment. It provides an important reference for research scientists and drug discovery companies.




Targeting Ion Channels for Drug Discovery: Emerging Challenges for High Throughput Screening Technologies


Book Description

Ligand and voltage-gated ion channels are highly regulated protein molecules that cross the cell membrane allowing ion flow from one side of the membrane to the other. They are ubiquitously expressed in human tissues and consist of one of the largest and best understood functional groups of proteins, with more than 400 members spanning nearly 1% of the human genome. They are involved in a variety of fundamental physiological processes, and their malfunction causes numerous diseases. In terms of the challenges faced in the effort to discover specific drugs in ancient and emerging diseases, ion channels are the third-largest class of target proteins after G-protein-coupled receptors (GPCRs) and kinases. 15% of small molecule drug targets have been reported to be voltage- or ligand-gated ion channels, resulting in approximately 150 new drug candidates in preclinical and clinical studies. Of the ion channel targeting drugs found on the market, these were identified more than a decade ago, and many of the current studies are at various stages of scientific approval. Overcoming these challenges has led the field of ion channel drug discovery to transform over the past 15 years through major advancements in genetic target detection, validation, structure-based drug design, and drug modeling of cell-based diseases.




Voltage Gated Sodium Channels


Book Description

A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.




Ion Channels in Health and Sickness


Book Description

Ion channels are proteins that make pores in the membranes of excitable cells present both in the brain and the body. These cells are not only responsible for converting chemical and mechanical stimuli into the electrical signals but are also liable for monitoring vital functions. All our activities, from the blinking of our eyes to the beating of our heart and all our senses from smell to sight, touch, taste and hearing are regulated by the ion channels. This book will take us on an expedition describing the role of ion channels in congenital and acquired diseases and the challenges and limitations scientist are facing in the development of drugs targeting these membrane proteins.




Ligand-gated Ion Channels as Drug Targets


Book Description

This program specifically deals with the basic concept of a ligand-gated ion channel embedded in the cell membrane. An attached screen shows further details of the gross structure of this type of receptor and that often, two agonist molecules must be bound for receptor activation. Some of the various sorts of ligand-gated ion channel channels found in the body are listed together with their major gating ligands and their speed of response is illustrated. The skeletal neuromuscular junction is used as an example of an excitatory ligand-gated ion channel and the GABAA receptor as an example of an inhibitory channel. The processes involved in the transmission of an impulse through junctions are explored, together with the transmembrane signal transduction mechanisms and their effects on current flow across the cell membrane. The effects of competitive and depolarising neuromuscular blockers are shown at the neuromuscular junction. A summary screen highlights the main points in the program and allows users to jump directly to any appropriate part of the program.




Voltage-gated Sodium Channels: Structure, Function and Channelopathies


Book Description

This book provides a timely state-of-the-art overview of voltage-gated sodium channels, their structure-function, their pharmacology and related diseases. Among the topics discussed are the structural basis of Na+ channel function, methodological advances in the study of Na+ channels, their pathophysiology and drugs and toxins interactions with these channels and their associated channelopathies.




Ion Channel Pharmacology


Book Description

The improved understanding of ion channel structure, achieved through the use of molecular biology techniques, has opened the way for the development of new drugs targeted at specific types of ion channels. This book provides a comprehensive, single-volume overview of the effects of different drugs and toxins on ionic channels. The first part of the book deals with the development of ion channels, while subsequent chapters detail the electrophysiological properties and pharmacology of eight different types of ion channels, including intracellular, cyclic nucleotide-gated, and receptor operated channels. Drug effects in various cell types, along with the potential use of channels in therapeutics, are discussed for each channel type. Comprehensive and up-to-date, Ion Channel Pharmacology is an essential reference for every investigator in this fast-growing area of research.