河豚毒素的药用研究进展

Advances in medicinal research on tetrodotoxin

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。

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 theα-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.