Sirek A, Sirek O V, Policova Z
Acta Diabetol Lat. 1975 May-Aug;12(3-4):199-201. doi: 10.1007/BF02581300.
Normal dogs were injected i.v. with 0.25 mg/kg sodium salt of HB 419 (glibenclamide) and plasma insulin concentrations were measured over a period of 2 hrs. When the animals were given a single i.v. injection of 0.2 mg/kg dihydroergotamine tartrate (DHE) 30 min prior to the administration of HB 419, the insulinogenic effect of the sulfonylurea was considerably amplified (192 muU/ml vs 34 muU/ml at 45 min). No augmentation of the insulinogenic effect of HB 419 was observed when the same experiments were conducted with 0.05, 0.025 or 0.01 mg/kg ergotamine tartrate. At the dose level of 0.1 mg/kg the insulinogenic effect of HB 419 was suppressed. Since the structural difference between these two ergot alkaloids consists of the presence or absence of the double bond at C9 and C10 of the lysergic acid moiety, it appears that saturation of this double bond is an essential structural requirement for DHE to function as an amplifier of sulfonylurea-stimulated insulin release.
给正常狗静脉注射0.25毫克/千克的HB 419（格列本脲）钠盐，并在2小时内测量血浆胰岛素浓度。当在给予HB 419前30分钟给动物单次静脉注射0.2毫克/千克酒石酸二氢麦角胺（DHE）时，磺脲类药物的促胰岛素分泌作用显著增强（45分钟时为192微单位/毫升，而未用DHE时为34微单位/毫升）。当用0.05、0.025或0.01毫克/千克酒石酸麦角胺进行相同实验时，未观察到HB 419促胰岛素分泌作用增强。在0.1毫克/千克剂量水平时，HB 419的促胰岛素分泌作用受到抑制。由于这两种麦角生物碱之间的结构差异在于麦角酸部分C9和C10处双键的有无，因此看来该双键的饱和是DHE作为磺脲类药物刺激胰岛素释放增强剂发挥作用的必要结构条件。
