Table 3.

Mechanisms of drug-induced hERG-K+ channel inhibition.

Drugs/Drug Classes	Direct Inhibition of hERG K+ Channel.	Inhibition of hERG K+ Channel Trafficking
Phenothiazines	+	-
Pentamidine	-	+
Geldalamicin	-	+
Ranolazine	+	-
Arsenic Trioxide	-	+
Fluoxetine, Norfluoxetine	+	+
Ketoconazole	+	+
Digitoxin, Ouabain, Digoxin	?	+
Sparfluoxacin,Ciprofloxacin, Ofloxacin	+	-
Amsacrin	+	-
Probucol	-	+
Donepezil	+	+
Tamoxifen, Endoxifen	+	+
Berberine	?	+
Citalopram,Escitalopram, Fluoxetine, Norfluoxetine	+	+
Atazanavir	+	+
Roxitromycin	+	+
Halofantrine,Chloroquine Mefloquine, Desbutyl-lumefantrine, Lumefantrine	+	?

Drug-induced inhibition of IKr currents can be achieved either by direct inhibition of potassium channels and/or by reducing the number of channels at the cell membrane. The latter is achieved by drug-induced impaired channel trafficking from the endoplasmic reticulum to the cell membrane. Data on drug-induced inhibition of channel trafficking is not available for all drugs.

Table taken with permission from Cubeddu [156]. Table content was modified and updated.