High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology.
Ion channels represent highly attractive targets for drug discovery and are implicated in a diverse range of disorders, in particular in the central nervous and cardiovascular systems. Moreover, assessment of cardiac ion-channel activity of new chemical entities is now an integral component of drug discovery programmes to assess potential for cardiovascular side effects. Despite their attractiveness as drug discovery targets ion channels remain an under-exploited target class, which is in large part due to the labour-intensive and low-throughput nature of patch-clamp electrophysiology. This Review provides an update on the current state-of-the-art for the various automated electrophysiology platforms that are now available and critically evaluates their impact in terms of ion-channel screening, lead optimization and the assessment of cardiac ion-channel safety liability.
Dunlop
John
J
Neuroscience Discovery Research, Wyeth Research, CN-8000, Princeton, New Jersey 08543, USA. Dunlopj@wyeth.com
Bowlby
Mark
M
Peri
Ravikumar
R
Vasilyev
Dmytro
D
Arias
Robert
R
D000818:Animals; D001331:Automation; D015195:Drug Design; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D018408:Patch-Clamp Techniques; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
D007473:Ion Channels; D008024:Ligands