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新型多巴胺类似物多培沙明在应激状态下对血小板功能的影响。

The effects of dopexamine, a new dopamine analogue, on platelet function in stress.

作者信息

Wagaine-Twabwe D, Hendra T J, Smith C C, Yudkin J S

机构信息

Academic Unit of Diabetes and Endocrinology, University College and Middlesex School of Medicine, Whittington Hospital, London.

出版信息

Br J Clin Pharmacol. 1990 Jul;30(1):87-95. doi: 10.1111/j.1365-2125.1990.tb03747.x.

Abstract
  1. Dopexamine is a novel analogue of dopamine which is free of alpha-adrenoceptor activity and is of therapeutic value in chronic heart failure. The effects of dopexamine on the in vitro function of platelets from 10 healthy subjects at rest, after exercise and after in vitro addition of adrenaline and noradrenaline were investigated. 2. Dopexamine in a wide range of concentrations (10(-9)M-10(-3)M) did not appear to function as an agonist on platelets either in whole blood or in PRP preparations. 3. Dopexamine caused a dose-dependent inhibition of agonist-induced platelet aggregation in both whole blood and PRP. The inhibitory effect of dopexamine was significantly greater in PRP than in whole blood, and significantly greater to adrenaline than to collagen or ADP as agonists in whole blood. 4. After exercise or after in vitro addition of adrenaline and noradrenaline at concentrations commonly seen in myocardial infarction, dopexamine produced similar levels of inhibition seen with platelets from resting subjects. 5. Dopexamine did not affect plasma catecholamine levels but caused an increase in intraplatelet noradrenaline levels. 6. This study suggests that dopexamine is unlikely adversely to affect the hyperaggregable state found in patients with cardiogenic shock after myocardial infarction.
摘要
  1. 多培沙明是一种新型多巴胺类似物,无α-肾上腺素能受体活性,对慢性心力衰竭具有治疗价值。研究了多培沙明对10名健康受试者静息状态、运动后以及体外添加肾上腺素和去甲肾上腺素后血小板体外功能的影响。2. 在广泛浓度范围(10⁻⁹M - 10⁻³M)内,多培沙明在全血或富血小板血浆(PRP)制剂中似乎都不能作为血小板激动剂发挥作用。3. 多培沙明在全血和PRP中均引起激动剂诱导的血小板聚集的剂量依赖性抑制。多培沙明在PRP中的抑制作用明显大于全血,并且在全血中作为激动剂时,对肾上腺素的抑制作用明显大于对胶原或二磷酸腺苷(ADP)的抑制作用。4. 在运动后或体外添加心肌梗死常见浓度的肾上腺素和去甲肾上腺素后,多培沙明产生的抑制水平与静息受试者的血小板相似。5. 多培沙明不影响血浆儿茶酚胺水平,但会导致血小板内去甲肾上腺素水平升高。6. 本研究表明,多培沙明不太可能对心肌梗死后心源性休克患者中发现的血小板高聚集状态产生不利影响。

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