Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review.
Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review.
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有机磷（OP）化合物是一种高毒性的人工合成化合物，既可用作杀虫剂，也可用作战争神经毒剂。它们对军人和平民都构成威胁。有机磷农药会影响神经系统，自20世纪30年代被发现以来，已造成至少500万人死亡。目前OP神经毒剂中毒的治疗一般采用肟类药物。然而，血脑屏障（BBB）仍然是肟向中枢神经系统（CNS）递送的挑战。这是因为几乎所有的大分子药物（包括肟）都不能通过血脑屏障到达中枢神经系统。肟中永久阳离子电荷的存在使得这些化合物在穿过血脑屏障时效率低下。因此，肟不能重新激活中枢神经系统中的乙酰胆碱酯酶（AChE）。利用目前在生理和病理条件下对BBB的结构和机制的理解，可以设计能够有效穿过BBB的肟和其他药物的递送系统。本文综述了能够穿过血脑屏障治疗OP中毒的肟类药物的最新开发策略。本文沿着介绍了肟类化合物的几种新的发展及其优缺点。这一审查可能是有益的，未来的发展方向，肟和其他药物输送系统进入中枢神经系统。有机磷（OP）化合物是一种高毒性的人工合成化合物，既可用作杀虫剂，也可用作战争神经毒剂。
Organophosphorus (OP) compounds are highly toxic synthetic compounds which have been used as pesticides and developed as warfare nerve agents. They represent a threat to both military and civilian populations. OP pesticides affect the nervous system and are thought to have caused at least 5 million deaths since their discovery in the 1930s. At present the treatment of OP nerve agent poisoning commonly involves the use of parenteral oximes. However, the blood brain barrier (BBB) remains a challenge in the delivery of oximes to the central nervous system (CNS). This is because almost all macromolecule drugs (including oximes) fail to pass through the BBB to reach the CNS structures. The presence of a permanent cationic charge in oximes has made these compounds inefficient in crossing the BBB. Thus, oximes are unable to reactivate acetylcholinesterase (AChE) in the CNS. Using current structural and mechanistic understanding of the BBB under both physiological and pathological conditions, it becomes possible to design delivery systems for oximes and other drugs that are able to cross the BBB effectively. This review summarises the recent strategies in the development of oximes which are capable of crossing the BBB to treat OP poisoning. Several new developments using oximes are reviewed along with their advantages and disadvantages. This review could be beneficial for future directions in the development of oxime and other drug delivery systems into the CNS. Organophosphorus (OP) compounds are highly toxic synthetic compounds which have been used as pesticides and developed as warfare nerve agents.
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影响因子：
7.3
作者：
Kalisiak, Jaroslaw;Ralph, Erik C.;Cashman, John R.
通讯作者：
Cashman, John R.
影响因子：
4.3
作者：
Antonijevic, Evica;Musilek, Kamil;Antonijevic, Biljana
通讯作者：
Antonijevic, Biljana
影响因子：
3.4
作者：
Antonijevic, Evica;Musilek, Kamil;Antonijevic, Biljana
通讯作者：
Antonijevic, Biljana
影响因子：
3.5
作者：
Joosen, Marloes J. A.;van der Schans, Marcel J.;van Helden, Herman P. M.
通讯作者：
van Helden, Herman P. M.
DOI：
10.1016/j.nano.2015.09.004
发表时间：
2016-01-01
影响因子：
5.4
作者：
Beloqui, Ana;Angeles Solinis, Maria;Preat, Veronique
通讯作者：
Preat, Veronique