钙通道阻滞剂的发现与发展。

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Godfraind T

钙通道阻滞剂的发现与发展。

Front Pharmacol. 2017年5月29日;8:286。doi: 10.3389 / fphar.2017.00286。eCollection 2017。

PubMed ID

28611661 (PubMed视图

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摘要

在20世纪60年代中期，对筛选作为冠状动脉扩张剂的分子进行的实验工作，使得后来被称为钙通道阻滞剂的药物发现了钙进入阻断的机制。本文综述了这些小分子直接与l型电压操作钙通道相互作用的科学研究。必威国际app它还报告了转化为对其治疗作用的理解的实验方法。钙在肌肉收缩中的重要性是由西德尼·林格发现的，他在1883年报告了这一事实。60年后，20世纪40年代初，Kamada(日本)和Heibrunn(美国)的实验引起了人们对钙在细胞内作用的兴趣。钙功能的药理学研究始于20世纪60年代中期，其在全球的治疗应用始于20世纪80年代。本报告的第一部分涉及心血管系统特别是孤立动脉的基本药理学。在“从钙拮抗剂到钙通道阻滞剂”一节中，回顾了在血管紧张素预收缩的冠状动脉床上体内筛选的一系列二苯基哌嗪类药物最初被命名为钙拮抗剂，这是基于它们在钙收缩的去极化动脉中的作用。对儿茶酚胺收缩动脉的研究表明，血管舒张是由于钙的进入被阻断。使用二氢吡啶进行的放射化学和电生理学研究允许它们的细胞目标被l型电压操作钙通道识别。 The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB) of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are important factors of their action. The high sensitivity of hypertensive animals is explained by the partial depolarization of their arteries. It is noted that they are arteriolar dilators and that they cannot be simply considered as vasodilators. The second part of this report provides key information about clinical usefulness of CCBs. A section is devoted to the controversy on their safety closed by the Allhat trial (2002). Sections are dedicated to their effect in cardiac ischemia, in cardiac arrhythmias, in atherosclerosis, in hypertension, and its complications. CCBs appear as the most commonly used for the treatment of cardiovascular diseases. As far as hypertension is concerned, globally the prevalence in adults aged 25 years and over was around 40% in 2008. Usefulness of CCBs is discussed on the basis of large clinical trials. At therapeutic dosage, they reduce the elevated blood pressure of hypertensive patients but don't change blood pressure of normotensive subjects, as was observed in animals. Those active on both L- and T-type channels are efficient in nephropathy. Alteration of cognitive function is a complication of hypertension recognized nowadays as eventually leading to dementia. This question is discussed together with the efficacy of CCBs in cognitive pathology. In the section entitled beyond the cardiovascular system, CCBs actions in migraine, neuropathic pain, and subarachnoid hemorrhage are reported. The final conclusions refer to long-term effects discovered in experimental animals that have not yet been clearly reported as being important in human pharmacotherapy.

引用本文的药物库数据

药物

硝苯地平

药物靶点

药物	目标	种类	生物	药理作用	行动
氨氯地平	电压依赖性n型钙通道(蛋白质组)	蛋白质组	人类	未知的	抑制剂	细节
硝苯地平	电压依赖性t型钙通道(蛋白质组)	蛋白质组	人类	未知的	抑制剂	细节