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Review Article

吡喹酮的作用机制：新药能否利用类似的机制？

卷 27, 期 5, 2020

页: [676 - 696] 页: 21

弟呕挨: 10.2174/0929867325666180926145537

价格: $65

摘要

吡喹酮（PZQ）是治疗血吸虫属蠕虫感染的首选药物。该药物有效，便宜且几乎没有副作用。然而，尽管其在数百万患者中使用了40多年，但其分子作用机理仍然难以捉摸。早期研究表明，PZQ会破坏蠕虫中的钙离子稳态，目前的共识是，它可以拮抗电压门控钙通道。假设这些通道的破坏导致不受控制的钙离子流入，导致不受控制的肌肉收缩和麻痹。但是，其他实验研究表明，肌球蛋白调节性轻链和腺苷的摄取在该药物的作用机理中起作用。假设电压门控钙通道确实代表了PZQ的主要分子靶标，则该药物的确切结合位点尚待确定。与其他常用的抗寄生虫药不同，文献中几乎没有关于PZQ耐药性的确切报道。缺乏有关PZQ分子机制的知识，削弱了我们预测抗药性可能如何产生的能力，也阻碍了我们尝试开发利用相同靶点的替代抗血吸虫病药物的尝试。已经鉴定出一些PZQ衍生物，它们也杀死或杀死培养物中的血吸虫。然而，这些都没有广泛用于临床。迫切需要对PZQ作用的分子机理进行基础研究。这样的研究将为抗血吸虫病药物的发现开辟新的途径。

关键词: 吡喹酮，血吸虫病，电压门控钙通道，被忽视的热带病，钙信号传导，药物作用机制。

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