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首页> 外文期刊>Journal of applied toxicology >Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review.
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Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review.

机译：一些肟的药代动力学和药效学及相关的治疗后果：严格的审查。

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Undoubtedly, the use of oximes represents real progress in counteracting intoxications with organophosphates (OP), through potentiating antidotal effects of atropine. The penetration extent of these compounds through the blood-brain barrier (BBB) to significantly reactivate phosphorylated or phosphonylated acetylcholinesterase (AChE) in the brain still remains a debatable issue. Penetration of biological barriers by oximes was investigated mainly through determination of several quantitative parameters characterizing digestive absorption and BBB penetration. A weak penetration of biological barriers could be concluded from the available experimental data. The functional parameters/therapeutic effects following the penetration of oximes through BBB, more precisely the antagonism of OP-induced seizures and hypothermia, prevention of brain damage and respiratory center protection, leading to the final end-point, the survival of intoxicated organisms, are of high interest. It seems obvious that oximes are weakly penetrating the BBB, with minimal brain AChE reactivation (<5%) in important functional areas, such as the ponto-medullar. The cerebral protection achieved through administration of oximes is only partial, without major impact on the antagonism of OP-induced seizures, hypothermia and respiratory center inhibition. The antidotal effects probably result from synergic effects of other PD properties, different from the brain AChE reactivation process. Oxime structures especially designed for enhanced BBB penetration, through potentiating the hydrophobic characteristics, more often produce neurotoxic effects. Certainly, obtaining oximes with broad action spectrum (active against all OP types) would make a sense, but certainly, such a target is not achievable only through the increase in their penetrability in the brain.
机译：无疑，肟的使用代表了通过增强阿托品的解毒作用来抵消有机磷酸酯（OP）中毒的真正进展。这些化合物穿过血脑屏障（BBB）的渗透程度以使大脑中的磷酸化或膦酰化乙酰胆碱酯酶（AChE）显着重新活化仍然是一个有争议的问题。主要通过确定表征消化吸收和血脑屏障渗透的几个定量参数研究了肟对生物屏障的渗透性。从现有的实验数据可以推断出生物屏障的弱渗透。肟通过BBB渗透后的功能参数/治疗效果，更确切地说是OP诱发的癫痫发作和体温过低的拮抗作用，预防脑损伤和呼吸中枢保护，从而导致最终终点，中毒生物的存活。很高的兴趣。似乎很明显，肟在BBB中的渗透较弱，在重要的功能区域（如桥脑）中脑AChE的再激活极低（<5％）。通过肟的给药实现的脑保护仅仅是部分的，对OP诱发的癫痫发作，体温过低和呼吸中枢抑制的拮抗作用没有重大影响。解毒作用可能是由其他PD特性的协同作用引起的，与大脑AChE的激活过程不同。专门为增强BBB渗透而设计的肟结构通过增强疏水特性而经常产生神经毒性作用。当然，获得具有广泛作用谱的肟（对所有OP类型均有效）是有道理的，但可以肯定的是，仅通过增加它们在大脑中的渗透性才能实现这一目标。

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