Anton A H, Berk A I
Res Commun Chem Pathol Pharmacol. 1982 Jan;35(1):79-94.
We studied the effect of oral hypoglycemic drugs on heart NE in normal and diabetic animals as a possible model for obtaining some insight into the mechanism for the alleged cardiotoxicity of these drugs in diabetic humans. The biguanides, but not the sulfonylureas, lowered NE in the hearts of rats and mice. Our results indicate this effect is not due to changes in blood glucose or a metabolite of the biguanides, but do not completely rule out an effect on biosynthesis or interference with the NE uptake pump in the adrenergic nerve endings. However, the data identify the biguanide portion of the molecule to be the active moiety and suggest that an indirect toxic effect of the drug probably is involved.
我们研究了口服降糖药对正常和糖尿病动物心脏去甲肾上腺素（NE）的影响，以此作为一种可能的模型，以便深入了解这些药物在糖尿病患者中所谓的心脏毒性机制。双胍类药物而非磺脲类药物可降低大鼠和小鼠心脏中的NE。我们的结果表明，这种作用并非由于血糖或双胍类药物代谢产物的变化所致，但也不能完全排除对生物合成的影响或对肾上腺素能神经末梢中NE摄取泵的干扰。然而，数据表明分子中的双胍部分是活性部分，并提示可能涉及药物的间接毒性作用。
