Glibenclamide actions

SLTR1/Kir6.2 Glibenclamide and glipizide that block pancreatic KAXP channels have been used for the treatment of type II diabetes. New class of insulin secretagogues includes repaglinide and nateglinide, which improve insulin secretion, action and reduce carbohydrate absorption. 

Glibenclamide has an intermediate duration of action. It is well absorbed with peak levels 4 hours after oral dosing. Its protein binding is about 90%. Glibenclamide is metabolized in the liver with an elimination half-life of 10 hours. However some of the metabolites which are excreted in the urine have hypoglycemic activity which makes glibenclamide... 

Glyburide (DiaBeta, Micronase, Glynase), also known as glibenclamide, is approximately 150 times as potent as tolbutamide on a molar basis and twice as potent as glipizide (discussed later). Glyburide is completely metabolized in the liver to two weakly active metabolites before excretion in the urine. Its average duration of action is 24 hours. 

Glibenclamide is a second generation sulfonylurea. There are two mechanisms of action for the lowering of the blood glucose ... 

Although evidence for channel activation explaining the mechanism of action of the KCAs was described in early publications [1, 61, 62], and was soon followed by the discovery of the blocking effects of glibenclamide (3),... 

Chopra, L.C., Twort, C.H.C. and Ward, J.P.T. (1992). Direct action of BRL 38227 and glibenclamide on intracellular calcium stores in cultured airway smooth muscle of rabbit. Br. J. Pharmacol. 105, 259-260. 

Xiong, Z., Kajioka, S., Sakai, T., Kitamura, K. and Kuriyama, H. (1991). Pinacidil inhibits the ryanodine-sensitive outward current and glibenclamide antagonises its action in cells from the rabbit portal vein. Br. J. Pharmacol. 102, 788-790. 

An important location of the sulphonylurea receptor is the ATP-sensitive K+ channel. Here, in contrast to ATP action, the binding site for sulphonylureas is not on the intracellular side but on the extracellular side of this channel (Niki et al., 1990). Niki et al. (1989, 1990) have provided evidence that ADP also binds to and competitively displaces glibenclamide from high-affinity HIT-cell sulphonylurea-binding sites. They also showed that ADP inhibited 86Rb+ efflux, elicited a rapid and sustained increase in [Ca2+]j and caused insulin secretion. Since ADP is unable to cross the cytoplasmic membrane, they concluded that ADP and sulphonylureas have common binding sites on the outer cell surface. 

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