The sage of the questionable cardiovascular safety of the sulphonylureas was given a nudge by the discovery that cardiac muscle and vascular smooth muscle express isoforms of the SUR2A and SUR2B. Sulphonylureas that contain a benzamido group (glibenclamide,glipizide,glimepiride) can bind to SURA2A and SUR2B whereas those without (e.g. tolbutamide,chlorpropamide and gliclazide) show very little interection with the cardiac and vascular SUR receptors. The effects of the KATP channel opener nicorandil (an anti-anginal drug with cardioprotective properties) are blocked by sulphonylureas that have a benzamido group. The clinical implications of these observations remain to be dethemined. Although very high concentrations of sulphonylureas can cause contraction of cardiac and vascular muscle, this is regarded as being unlikely to be clinically significant effect at therapeutic drug concentrations. Nonetheless, on the basis of adverse clinical experiences in high-risk patients, some high profile authorities continue to advocate that sulphonylurea use be kept to a minimum in patients with overt coronary artery disease.