Moretto A
Istituto di Medicina del Lavoro, Università degli Studi di Padova, Italy.
Toxicol Lett. 1998 Dec 28;102-103:509-13. doi: 10.1016/s0378-4274(98)00245-8.
Several organophosphorus compounds (OP) and carbamates (CA) are used as insecticides or warfare agents (OPs only). Their acute toxic effect in the central and peripheral nervous system is due to inhibition of acetylcholinesterase (AChE) at nerve endings which causes accumulation of acetylcholine and consequently overstimulation of the nicotinic and muscarinic receptors. The cholinergic syndrome appears at approximately 50% AChe inhibition whereas death is believed to occur at > 90%. Inhibition of AChE (phosphorylation) by most OPs is irreversible whereas CAs reversibly inhibit AChE (spontaneous reactivation with a t(1/2) of minutes); dimethylphosphorylated AChE partially and slowly (t(1/2) = 1-2 h) reactivates. Although long-term, mild neurobehavioural changes of questionable significance have been reported in some instances, recovery from the cholinergic syndrome appears to be complete, unless lesions develop in the central nervous system as a consequence of either convulsions or anoxia. Certain OPs and CAs have been reported to interact with cholinergic receptors in vitro. The toxicological relevance of these interactions is still not clear. Certain OPs cause OP-induced delayed polyneuropathy (OPIDP) which develops 2-5 weeks after an acute poisoning. The molecular target is believed to be neuropathy target esterase (NTE). OP insecticides are more potent AChE inhibitors rather than NTE inhibitors and therefore, the dose required to cause OPIDP is much higher than that causing the cholinergic syndrome. In the experimental animal, OPIDP is associated with > 70% NTE inhibition after single or repeated exposures. The threshold in man is not known, although there are indications that it is similar. Some non-neuropathic esterase inhibitors (OPs, CAs, sulfonyl fluorides) exacerbate the clinical outcome of OPIDP and other chemical axonopathies, and of nerve crush. The phenomenon has been called promotion and has so far been observed in experimental animals only.
几种有机磷化合物（OP）和氨基甲酸酯（CA）被用作杀虫剂或战争毒剂（仅OP）。它们在中枢和外周神经系统的急性毒性作用是由于抑制神经末梢的乙酰胆碱酯酶（AChE），导致乙酰胆碱积累，进而过度刺激烟碱样和毒蕈碱样受体。胆碱能综合征在AChE抑制约50%时出现，而死亡被认为发生在抑制>90%时。大多数OP对AChE的抑制（磷酸化）是不可逆的，而CA可逆地抑制AChE（自发重新激活，半衰期为几分钟）；二甲基磷酸化的AChE部分且缓慢地（半衰期 = 1 - 2小时）重新激活。尽管在某些情况下报告了长期、轻微且意义存疑的神经行为变化，但胆碱能综合征的恢复似乎是完全的，除非由于惊厥或缺氧导致中枢神经系统出现病变。某些OP和CA在体外已被报道与胆碱能受体相互作用。这些相互作用的毒理学相关性仍不清楚。某些OP会导致OP诱导的迟发性多发性神经病（OPIDP），在急性中毒后2 - 5周出现。分子靶点被认为是神经病靶酯酶（NTE）。OP杀虫剂是更强效的AChE抑制剂而非NTE抑制剂，因此，导致OPIDP所需的剂量远高于导致胆碱能综合征的剂量。在实验动物中，单次或重复暴露后，OPIDP与NTE抑制>70%相关。人类的阈值尚不清楚，尽管有迹象表明与动物相似。一些非神经性酯酶抑制剂（OP、CA、磺酰氟）会加重OPIDP和其他化学性轴索性神经病以及神经挤压伤的临床后果。这种现象被称为促进作用，迄今为止仅在实验动物中观察到。
