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Tetramethylenedisulfotetramine neurotoxicity: What have we learned in the past 70 years?
Neurobiology of Disease ( IF 6.1 ) Pub Date : 2019-06-06 , DOI: 10.1016/j.nbd.2019.104491
Marcela Lauková 1 , Jana Velíšková 2 , Libor Velíšek 3 , Michael P Shakarjian 4
Affiliation  

Tetramethylenedisulfotetramine (tetramine, TETS, TMDT) is a seizure-producing neurotoxic chemical formed by the condensation of sulfamide and formaldehyde. Serendipitously discovered through an occupational exposure in 1949, it was promoted as a rodenticide but later banned worldwide due to its danger to human health. However, exceptional activity of the agent against rodent pests resulted in its clandestine manufacture with large numbers of inadvertent, intentional, and mass poisonings, which continue to this day. Facile synthesis, extreme potency, persistence, lack of odor, color, and taste identify it as an effective food adulterant and potential chemical agent of terror. No known antidote or targeted treatment is currently available. In this review we examine the origins of tetramethylenedisulfotetramine, from its identification as a neurotoxicant 70 years ago, through early research, to the most recent findings including the risk it poses in the post-911 world. Included is the information known regarding its in vitro pharmacology as a GABAA receptor channel antagonist, the toxic syndrome it produces in vivo, and its effect upon vulnerable populations. We also summarize the available information about potential therapeutic countermeasures and treatment strategies as well as the contribution of clinical development of TMDT poisoning to our understanding of epileptogenesis. Finally we identify gaps in our knowledge and suggest potentially fruitful directions for continued research on this dangerous, yet intriguing compound.

中文翻译:

四亚甲基二磺四胺神经毒性:在过去的70年中,我们学到了什么?

四亚甲基二磺基四胺(四胺,TETS,TMDT)是一种会引起癫痫发作的神经毒性化学物质,它是由亚磺酰胺和甲醛的缩合形成的。1949年通过职业暴露偶然发现,被推广为灭鼠剂,但由于其对人体健康的危害,后来在全球范围内被禁止使用。但是,该试剂对啮齿动物害虫的出色活性导致其秘密制造,并造成大量无意,故意和大规模中毒,这种情况一直持续到今天。简便的合成,极强的效力,持久性,没有气味,颜色和味道,使它成为有效的掺假食品和恐怖的潜在化学制剂。当前没有已知的解毒剂或靶向治疗方法。在这篇评论中,我们研究了四亚甲基二磺基四胺的起源,从70年前被鉴定为神经毒剂到早期研究,再到最新发现,包括它对911后世界造成的风险。其中包括有关其作为GABAA受体通道拮抗剂的体外药理学,其在体内产生的毒性综合症及其对弱势人群的影响的已知信息。我们还总结了有关潜在治疗对策和治疗策略的可用信息,以及TMDT中毒的临床发展对我们对癫痫发生认识的贡献。最后,我们确定了我们的知识差距,并为继续研究这种危险而有趣的化合物提供了可能富有成果的指导。其中包括有关其作为GABAA受体通道拮抗剂的体外药理学,其在体内产生的毒性综合症及其对弱势人群的影响的已知信息。我们还总结了有关潜在治疗对策和治疗策略的可用信息,以及TMDT中毒的临床发展对我们对癫痫发生认识的贡献。最后,我们确定了我们的知识差距,并为继续研究这种危险而有趣的化合物提供了可能富有成果的指导。其中包括有关其作为GABAA受体通道拮抗剂的体外药理学,其在体内产生的毒性综合症及其对弱势人群的影响的已知信息。我们还总结了有关潜在治疗对策和治疗策略的可用信息,以及TMDT中毒的临床发展对我们对癫痫发生认识的贡献。最后,我们确定了我们的知识差距,并为继续研究这种危险而有趣的化合物提供了可能富有成果的指导。我们还总结了有关潜在治疗对策和治疗策略的可用信息,以及TMDT中毒的临床发展对我们对癫痫发生认识的贡献。最后,我们确定了我们的知识差距,并为继续研究这种危险而有趣的化合物提供了可能富有成果的指导。我们还总结了有关潜在治疗对策和治疗策略的可用信息,以及TMDT中毒的临床发展对我们对癫痫发生认识的贡献。最后,我们确定了我们的知识差距,并为继续研究这种危险而有趣的化合物提供了可能富有成果的指导。
更新日期:2019-06-06
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