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[3-羟基吡啶和琥珀酸衍生物的抗缺氧作用及其在四氧嘧啶糖尿病中的益智作用]

[Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

作者信息

Volchegorskiĭ I A, Rassokhina L M, Miroshnichenko I Iu

出版信息

Eksp Klin Farmakol. 2011;74(12):27-32.

PMID:22379879
Abstract

Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

摘要

在四氧嘧啶诱导的糖尿病大鼠中,研究了3-羟基吡啶与琥珀酸衍生物(依莫昔平、雷安匹林和美西多芬)的抗缺氧作用及其对条件学习、血糖和血脂的影响。同时,研究了被视为糖尿病神经病变治疗“金标准”的α-硫辛酸的类似关系。结果表明,小鼠单次给予相当于人类治疗剂量范围的依莫昔平和美西多芬,可产生抗缺氧作用,表现为试验动物对急性低氧性缺氧的抵抗力增强。α-硫辛酸的抗缺氧作用程度低于依莫昔平和美西多芬。雷安匹林未表现出这种作用。在四氧嘧啶糖尿病大鼠中,连续7天或14天给予相当于人类治疗剂量范围的依莫昔平、雷安匹林、美西多芬和α-硫辛酸,可纠正条件学习障碍,且与这些药物的抗缺氧活性直接相关。依莫昔平、美西多芬和α-硫辛酸的促智作用的产生与四氧嘧啶糖尿病大鼠的高血糖和高血脂的降低有关。雷安匹林的促智作用伴随着短暂的降血糖作用和血脂异常的加重。所研究药物的抗缺氧活性决定了它们血脂作用的方向和表现,但与这些药物对四氧嘧啶糖尿病试验动物的降血糖作用无关。

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引用本文的文献

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Efficacy and safety of the combined metabolic medication, containing inosine, nicotinamide, riboflavin and succinic acid, for the treatment of diabetic neuropathy: a multicenter randomized, double-blind, placebo-controlled parallel group clinical trial (CYLINDER).含肌苷、烟酰胺、核黄素和琥珀酸的联合代谢药物治疗糖尿病周围神经病变的疗效和安全性:一项多中心、随机、双盲、安慰剂对照平行分组临床试验(CYLINDER)。
BMJ Open Diabetes Res Care. 2022 Jun;10(3). doi: 10.1136/bmjdrc-2022-002785.