Sulfonylureas: Pharmacokinetics in Animal Experiments

The Impact of ATP-Sensitive K+ Channel Subtype Selectivity of Insulin Secretagogues for the Coronary Vasculature and the Myocardium

“…The generation of mice in which the genes for the K ATP channel subunits were deleted have shed new light on the diverse functions of the K ATP channels in various tissues in physiological and pathophysiological conditions (1). In brain, K ATP channels are involved in actions as diverse as the control of glucose homeostasis and the regulation of neuronal excitability in hypoxia (1); however, the insulin secretagogues do not cross the blood-brain barrier easily enough to affect these channels at therapeutic plasma levels (4). In several vascular beds, the K ATP channel in the vascular myocytes is involved in the regulation of vessel tone; opening is triggered in particular by stimuli increasing cAMP (5).…”

“…K ATP channels are composed of two types of subunits, inwardly rectifying K ϩ channels (Kir6.x) and sulfonylurea receptors (SURx), arranged as tetradimeric complexes, (Kir6.x/SURx) 4 ( Fig. 1) (rev.…”