| Summary: | Amongst his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918-2016) provided a classification of anti-arrhythmic drugs that remains central to their clinical use. On this centenary of his birth we survey the implications of subsequent discoveries concerning sarcolemmal, sarcoplasmic reticular and cytosolic biomolecules, to develop an expanded but pragmatic classification that encompasses approved and potential anti-arrhythmic drugs. We first consider the range of pharmacological targets, tracking these through to cellular electrophysiological effects. We retain the original Vaughan Williams classes I to IV, but subcategorise these divisions in the light of more recent developments, including existence of Na+ current components (for Class 1), advances in autonomic (often G-protein-mediated) signalling (for Class II), K+ channel subspecies (for Class III), and novel molecular targets related to Ca2+ homeostasis (for Class IV). We introduce new classes based on additional targets, including channels involved in automaticity, mechanically sensitive ion channels, connexins controlling electrotonic cell coupling, and molecules underlying longer term signalling processes affecting structural remodelling. Inclusion of this widened range of targets and their physiological sequelae provides a framework for a modernised classification of established anti-arrhythmic drugs based on their pharmacological targets. The revised classification allows for existence of multiple drug targets/actions and for adverse, sometimes actually pro-arrhythmic effects. The new scheme also aids classification of novel drugs under investigation. We emerge with a revised classification preserving the simplicity of the original Vaughan Williams framework whilst aiding our understanding and clinical management of cardiac arrhythmic events, and facilitating future developments in this area.
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