药理方法纠正离子传输缺陷在囊性纤维化。

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药理方法纠正离子传输缺陷在囊性纤维化。

和医学。2003;2(5):413 - 31所示。doi: 10.1007 / BF03256668。

PubMed ID

14719993 (在PubMed

]

文摘

囊性纤维化(CF)是一种致命的膜蛋白的突变引起的遗传性疾病,囊性纤维化跨膜电导调节(雌性生殖道),主要(但不仅限于)函数作为氯通道。主要的临床症状是慢性阻塞性肺病、负责大部分的发病率和死亡率与CF有关,和胰腺功能不全。大约1000突变的CFTR基因编码检测是目前已知;最常见的,存在于绝大多数的患者(Delta508)导致苯丙氨酸的删除在508位置。这种突变的CFTR异常的检测不是运往膜但ubiquitin-proteasome退化的途径。本综述的目的是提供一个概述目前使用的药物策略的尝试克服CF的离子传输缺陷。CF开发药物治疗策略之一是抑制DeltaF508-CFTR分解通过干扰雌性生殖道的监护人参与折叠。至少在体外系统,这可以通过钠phenylbutyrate,或S-nitrosoglutathione (GSNO),以及染料木黄酮和苯并[c] quinolizinium化合物。也可以刺激雌性生殖道或其变异形式,存在于质膜时,使用黄嘌呤,染料木素,和其他各种化合物,如benzamidizoles和苯并恶唑、苯并[c]或phenantrolines quinolizinium化合物。实验结果并不总是明确的和负面影响已经不完全测试。一些临床试验已经完成苯丁酸钠,GSNO和染料木素,主要是在对其他疾病,结果证明这些药物是相当良好的耐受性。 Their efficiency in the treatment of CF has not yet been demonstrated, however. An alternative strategy is to compensate for the defective chloride transport by CFTR by stimulation of other chloride channels. This can be done via purinergic receptors. A phase I study using a stable uridine triphosphate analog has recently been completed. A second alternative strategy is to attempt to maintain hydration of the airway mucus by inhibiting Na(+) uptake by the epithelial Na(+) channel using amiloride or stable analogs of amiloride. Clinical tests so far have been inconclusive. A number of other suggestions are currently being explored. The minority of patients with CF who have a stop mutation may benefit from treatment with gentamicin. The difficulties in finding a pharmacologic treatment for CF may be due to the fact that CFTR has additional functions besides chloride transport, and interfering with CFTR biosynthesis or activation implies interference with central cellular processes, which may have undesirable adverse effects.

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药物靶点

药物	目标	类	生物	药理作用	行动
染料木黄酮	囊性纤维化跨膜电导调节	蛋白质	人类	未知的	激活剂	细节