Campbell D B, Lavielle R, Nathan C
Servier Research and Development, Fulmer, Slough, U.K.
Diabetes Res Clin Pract. 1991;14 Suppl 2:S21-36. doi: 10.1016/0168-8227(91)90005-x.
Gliclazide is a sulphonylurea drug with an intermediate half-life of around 11 hours. It is extensively metabolised, and renal clearance accounts for only 4% of total drug clearance. The molecule contains an azabicyclo-octyl group which confers special properties on the basic sulphonylurea moiety. Gliclazide stimulates insulin secretion through the beta cell sulphonylurea receptor, and possibly through a direct effect on intracellular calcium transport. It specifically improves the abnormal first phase insulin release in type 2 diabetes, and also has an effect on the second phase. This pattern of insulin release is thought to explain the lower incidence of hypoglycaemic episodes and weight gain compared with some other sulphonylureas. There is also a reduction in hepatic glucose production and improvement in glucose clearance, without changes in insulin receptors. This suggests a possible post-receptor effect on insulin action, perhaps by stimulation of hepatic fructose-2,6-bisphosphatase and muscle glycogen synthase. Gliclazide reduces platelet adhesion, aggregation and hyperactivity and increases fibrinolysis. These actions, thought to be independent of its hypoglycaemic activity, may make gliclazide useful in halting the progression of diabetic microangiopathy.
格列齐特是一种半衰期约为11小时的磺脲类药物。它代谢广泛，肾清除率仅占总药物清除率的4%。该分子含有一个氮杂双环辛基，赋予了基本磺脲部分特殊性质。格列齐特通过β细胞磺脲受体刺激胰岛素分泌，也可能通过对细胞内钙转运的直接作用来实现。它能特异性改善2型糖尿病患者异常的第一相胰岛素释放，对第二相也有作用。这种胰岛素释放模式被认为可以解释与其他一些磺脲类药物相比，其低血糖发作和体重增加发生率较低的原因。同时，它还能减少肝脏葡萄糖生成并改善葡萄糖清除率，而胰岛素受体无变化。这表明其可能对胰岛素作用有受体后效应，或许是通过刺激肝脏果糖-2,6-二磷酸酶和肌肉糖原合酶来实现。格列齐特可降低血小板黏附、聚集和活性亢进，并增强纤维蛋白溶解作用。这些作用被认为与其降血糖活性无关，可能使格列齐特在阻止糖尿病微血管病变进展方面发挥作用。
