1 The aim of this study was to determine whether antimalarial agents inhibit ATP-sensitive potassium (K-ATP) channels and thereby contribute to the observed side-effects of these drugs.2 Mefloquine (10-100 muM), but not artenusate (100 muM), stimulated insulin release from pancreatic islets in vitvo.3 Macroscopic K-ATP currents were studied in inside-out patches excised from Xenopus oocytes expressing cloned K-ATP channels.4 Mefloquine (IC50 similar to3 muM), quinine (IC50 similar to3 muM), and chloroquine inhibited the pancreatic beta -cell type of KATP channel Kir6.2/SUR1. Artenusate (100 muM) was without effect.5 Mefloquine and quinine also blocked a truncated form of Kir6.2 (Kir6.2 Delta C36) when expressed in the absence of SUR1. The extent of block was similar to that observed for Kir6.2/SUR1 currents.6 Our results suggest that inhibition of the beta -cell K-ATP channel accounts for the ability of quinoline-based antimalarial drugs to stimulate insulin secretion, and thereby produce hypoglycaemia.7 The results also indicate that quinoline-based antimalarial agents inhibit K-ATP channels by interaction with the Kir6.2 subunit. This subunit is common to beta -cell, neuronal, cardiac, skeletal muscle, and some smooth muscle K-ATP channels suggesting that K-ATP channel inhibition may contribute to the other side effects of these drugs, which include cardiac conduction abnormalities and neuropsychiatric disturbances.
Gribble, F. M., Davis, T., Higham, C. E., Clark, A., & Ashcroft, F. M. (2000). The antimalarial agent mefloquine inhibits ATP-sensitive K-channels. British Journal of Pharmacology, 131(4), 756-760. https://doi.org/10.1038/sj.bjp.0703638