Gliclazide

Bretschneider, H.,Grassmavr, K., Hohenlohe-Oehringen, K. and Grussner, A. U.S. Patent 3,654 57 April 4, 1972 assigned to Hoffmann-La Roche Inc, 

Chemical Name 1-(hexahydrocyclopenta(c] pyrrol-2(1 H)-yl)-3-(p-tolylsulfonyl)urea Common Name N-(4-methylbenzenesulfonyl)-N -(3-azabicyclo(3.3.0] -3-octyl)urea Structural Formula  

DIamicron Diamicron Diamicron Diamicron Diamicron Dram ion 

To a suspension containing 4.86 parts of 4-methylbenzenesulfonyl urethane (MP 80° to 82°C) and 36 parts of anhydrous toluene there are rapidly added 2.5 parts of N-amino-3-azabicyclo(3.3.0)octane (BP/18 mm = 86°C). The reaction mixture is heated under reflux for 1 hour. The resulting ciear solution crystallizes on cooling. The crystals are filtered, washed with 2 parts of toluene, then recrystallized from anhydrous ethanol. There are obtained 3.8 parts of the desired product, MP 180° to 182°C. 

Beregi, L Hugon, P. and Duhault, J. U.S. Patent 3,501,495 March 17, 1970 assigned to Science Union et Cie, Societe Francaise de Recherche Medicale, France 

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Sulphonylureas Chlorpropamide, glibenclamideb, gliclazide, glimepiride, glipizide, gliquidone, tolazamide, tolbutamide Stimulate insulin secretion (typically 6-24 h) Oral... 

Several studies have demonstrated that treatment of diabetic patients with the sulphonylurea, gliclazide, is associated with a fall in lipid peroxidation, protein fluorescence and beneficial effects on platelet function (Florkowski et al., 1988 Jennings et al., 1992). These changes were seen to be independent of changes in giycaemic control. 

Rosiglitazone is a thiazolidinedione that can be used in combination with metformin or a sulphonylurea such as gliclazide. Rosiglitazone should be administered with caution in patients with cardiovascular disease. 

Gliclazide is a sulphonylurea. In general, diabetic patients are switched over to insulin during pregnancy. Sulphonylureas should be stopped at least 2 days... 

Gliclazide is slowly absorbed. It is metabolized and excreted in the urine, in part as unchanged drug with an elimination half-life of 6-14 hours. Its duration of action is about 12 hours. Glicazide reduces platelet adhesiveness and increases fibrinolytic activity. This could be of importance as both factors have been implicated in the pathogenesis of the longterm organ failure in diabetes. 

However additional peculiarities are found in some preparations. Glimepiride results in lower insulin and C-peptide levels with similar glucose control, probably due its greater extrapancreatic effect on insulin target tissues. Gliclazide has a lower secondary failure rate than glyburide or glipizide. 

Gliclazide reduces blood glucose levels by correcting both defective insulin secretion and peripheral insulin resistance. 

Gliclazide also has been reported to reduce plasma cholesterol and triglyceride levels after repeated administration. 

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