GIRK channels are increasingly recognized as important targets for drug design focused on diseases such as epilepsy and addiction. While current studies employed methods that specifically target GIRK channels, historically that was not the case. Typically, drugs developed for other diseases, such as FDA-approved drugs, were found to have an effect on GIRK channels. The off-target effects of drugs with other primary targets or multiple targets was a common theme among the first generation of compounds that modulate GIRK channels, as described for channel activators (Box 1) and inhibitors (Box 2). These channel modulators provided important information about GIRK channel function and pharmacology. As the lack of specificity could limit their potential clinical use, this review will focus on more GIRK-selective compounds.
