HMR 1883
From Wikipedia, the free encyclopedia
HMR 1883 (1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3 methylthiourea) and its sodium salt HMR 1098, are experimental anti-arrhythmic drugs classified as sulfonylurea compounds.[1] Their main purpose is to treat ventricular fibrillation caused by myocardial ischemia. They were synthesized via structural modifications to glibenclamide, an antidiabetic drug.[1] Both HMR 1883 and glibenclamide act by inactivating the ATP-sensitive potassium channels (KATP) responsible for potassium efflux.[2] Unlike glibenclamide, HMR 1883 has been suggested to target selectively the Kir6.2/SUR2A KATP subtype, found mostly in the membranes of cardiac cells.[3] However, data showing that HMR 1098 inhibits the Kir6.2/SUR1 KATP subtype found in insulin-secreting pancreatic beta cells challenges this view.[4]
Hypoxia provokes potassium efflux from cardiac muscles cells via the activation of ATP-sensitive potassium channels (KATP).[5] Potassium efflux from cardiac cells decreases action potential duration and results in non-uniform repolarization of the cardiac cells.[6] The heterogeneous repolarization of the cardiac tissue permits reentry of action potentials into conducting pathways, which manifests as malignant arrhythmias in the heart.[6] HMR 1883 is a cardioselective ATP-sensitive potassium channel antagonist that prevents the potassium efflux, hence correcting the non-uniform refractory period in the ischemic tissue. A uniform refractory period corrects the conductance problems in the heart and prevents the re-entry arrhythmias.