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河豚毒素(TTX)是一种海洋生物毒素。TTX首次在河豚中提取得到,而后在多个海洋动植物和陆地部分动物中发现。TTX是一种电压门控钠通道(VGSCs)的阻滞剂,能够选择性地与VGSCs外前庭上的α-亚基结合,阻止钠离子进入通道,从而产生药理活性。TTX具有镇痛、戒毒、抗心律失常等作用,此外,还有降低心血管药物不良反应的作用。目前已经有许多TTX在研制剂,研究者也正在针对TTX的剂型进行研究。本文就TTX的来源、结构性质、作用机制、药理活性、在研剂型进行综述,旨在为下一步TTX的药用开发提供参考。
Advances in medicinal research on tetrodotoxin
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摘要: 河豚毒素(TTX)是在河豚鱼和其他海洋动物中发现的一种神经毒素。它是一种电压门控钠通道(VGSCs)阻滞剂,能够选择性地与VGSCs外前庭上的α-亚基结合,阻止钠离子进入通道,从而产生药理活性。作为典型的钠离子通道阻滞剂,TTX具有显著的镇痛作用。TTX能够选择性地阻断Na+通道而不影响其他离子通道,减少了常用抗心律失常药物引起不良反应的概率,降低了用药风险。此外,TTX在戒毒等方面亦有显著作用。因此,TTX具有很大的成药潜力。本文对河豚毒素的结构与性质、作用机制、药理活性和在研制剂进行综述,为其成药性评价研究和在药学领域的应用提供概要性支撑。Abstract: Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine organisms. It has been used as an inhibitor of voltage-gated sodium channels (VGSCs), which could selectively bind to the α-subunit on the outer vestibule of VGSCs, preventing sodium ions from entering the channel, resulting in pharmacological activities. As a typical sodium channel blocker, TTX shows a significant analgesic effect. TTX could selectively block Na+ channels without affecting other ion channels, therefore it could reduce the probability of adverse reactions caused by commonly used antiarrhythmic drugs. In addition, TTX has a significant role in detoxification and prevention of renal failure, so TTX has great potential as a medicine. The structure and physicochemical properties, mechanism of action, pharmacological activities and preparations of tetrodotoxin have been reviewed in this paper, so as to provide a general support for the evaluation of its druggability and application in the field of pharmacy.
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Key words:
- tetrodotoxin /
- neurotoxin /
- analgesic effect /
- pharmacological activity /
- preparation
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