The Pharmacology of Indomethacin
The Pharmacology of Indomethacin
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DOI：
10.1111/head.12769
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发表时间：
2016-02-01
期刊：
影响因子：
5
通讯作者：
Lucas, Sylvia
中科院分区：
文献类型：
--
作者：
Lucas, Sylvia
背景50多年前，在寻找有效的抗炎和镇痛药物的巨大努力中，吲哚美辛作为一种非常有效的非甾体抗炎药（NSAID）出现。20世纪60年代，乙酸衍生物发展成吲哚美辛、双氯芬酸和舒林酸，丙酸衍生物发展成布洛芬、萘普生和酮洛芬。吲哚美辛可能是这些化合物中最有效的，也是最早进入临床试验的化合物之一。吲哚美辛是最早用于治疗偏头痛和最终被称为吲哚美辛反应性头痛疾病的头痛的NSAID药物之一，这并不奇怪。潜在的药物代谢动力学和生物力学之间的差异吲哚美辛和其他非甾体抗炎药是巨大的临床和研究的兴趣来解释这一observation.Methods/ResultsThe本文章总结了吲哚美辛的药理学特性，包括药代动力学，特别注意其分布到中枢神经系统，不良反应，药物相互作用，和机制的行动。数据强调吲哚美辛和其他非甾体抗炎药之间的生物力学差异。吲哚美辛在孕妇和哺乳期妇女的使用review.ConclusionsNSAIDs容易进入大脑，但其高蛋白结合限制绝对量的进入。所有的工作类似的非选择性或选择性环氧合酶抑制剂，但吲哚美辛可能有更有效的血管收缩活性和独特的直接神经元或一氧化氮依赖性抑制途径的活动。
BackgroundOver 50 years ago, indomethacin emerged as an extremely potent non-steroidal anti-inflammatory drug (NSAID) during a massive effort to find effective anti-inflammatory and analgesic medications. The 1960s saw acetic acid derivatives developed into indomethacin, diclofenac, and sulindac, and propionic derivatives into ibuprofen, naproxen, and ketoprofen. Indomethacin was likely the most potent of these compounds and one of the earliest to enter clinical trials. It is not surprising that indomethacin was among the first of the NSAID medications to be used in treatment of migraine and for headaches that eventually became known as indomethacin-responsive headache disorders. Potential pharmacokinetic and bio-mechanistic differences between indomethacin and other NSAIDs are of great clinical and research interest to explain this observation.Methods/ResultsThe present article summarizes pharmacologic properties of indomethacin, including pharmacokinetics with particular attention to its distribution into the central nervous system, adverse effects, drug interactions, and mechanisms of action. Data are emphasized where differences in biomechanisms are found between indomethacin and other NSAIDs. The use of indomethacin in pregnant and lactating women is reviewed.ConclusionsNSAIDs easily enter the brain, but their high protein binding limits absolute amount of entry. All work similarly as either nonselective or selective cyclooxygenase inhibitors, but indomethacin may have more potent vasoconstrictive activity and unique direct neuronal or nitric oxide-dependent inhibitory pathway activity.