ABSTRACT
To date very few drugs have been developed as potassium channel blocker (KCBs ). This may seem to be a strange introduction to a chapter concerned with the Structure-Activity Relationships (SAR) of such agents but it is nevertheless true. In the main, compounds in this chapter had originally been developed with various therapeutic goals in mind and were screened accordingly in an in vitro or an in vivo model which reflected this goal. Subsequently, the lead compounds in the various series were found to be KCBs and the responses of these lead compounds at various K channels were then examined in some detail. This distinction may seem to be rather arbitrary and inconsequential, but it means that the derived SAR of such compounds not only reflect their abilities as KCBs, but also other factors as well. The presence of lipophilic groups, for example may reflect the need for a drug to cross a membrane rather than to locate a hydrophobic pocket on a receptor and, for these compounds, it is not possible to determine a priori what the interactions at the receptor level actually are. In spite of this, the SAR discussed here will assume that it is concerned with activity at the channels. More recently, drugs are being developed from their inception with due consideration both to their primary K channel blocking effects and with their eventual use in mind.
