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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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