Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Chem Biol Interact. 2011 Apr 25;190(2-3):79-83. doi: 10.1016/j.cbi.2011.02.022. Epub 2011 Feb 25.
The simultaneous use of the repellent DEET, pyridostigmine, and organophosphorus pesticides has been assumed as a potential cause for the Gulf War Illness and combinations have been tested in different animal models. However, human in vitro data on interactions of DEET with other compounds are scarce and provoked the present in vitro study scrutinizing the interactions of DEET, pyridostigmine and pesticides with human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE). DEET showed to be a weak and reversible inhibitor of hAChE and hBChE. The IC(50) of DEET was calculated to be 21.7mM DEET for hAChE and 3.2mM DEET for hBChE. The determination of the inhibition kinetics of pyridostigmine, malaoxon and chlorpyrifos oxon with hAChE in the presence of 5mM DEET resulted in a moderate reduction of the inhibition rate constant k(i). The decarbamoylation velocity of pyridostigmine-inhibited hAChE was not affected by DEET. In conclusion, the in vitro investigation of interactions between human cholinesterases, DEET, pyridostigmine, malaoxon and chlorpyrifos oxon showed a weak inhibition of hAChE and hBChE by DEET. The inhibitory potency of the tested cholinesterase inhibitors was not enhanced by DEET and it did not affect the regeneration velocity of pyridostigmine-inhibited AChE. Hence, this in vitro study does not give any evidence of a synergistic effect of the tested compounds on human cholinesterases.
避蚊胺（DEET）、吡咯烷酮和有机磷杀虫剂的同时使用被认为是海湾战争综合征的一个潜在原因，并且这些组合已在不同的动物模型中进行了测试。然而，关于 DEET 与其他化合物相互作用的人体体外数据很少，这引发了本体外研究，仔细研究了 DEET、吡咯烷酮和杀虫剂与人乙酰胆碱酯酶（hAChE）和丁酰胆碱酯酶（hBChE）的相互作用。DEET 被证明是 hAChE 和 hBChE 的弱可逆抑制剂。DEET 对 hAChE 和 hBChE 的 IC50 分别计算为 21.7mM DEET 和 3.2mM DEET。在 5mM DEET 存在的情况下，测定吡咯烷酮、马拉氧磷和氯菊酯氧磷对 hAChE 的抑制动力学，结果导致抑制速率常数 k(i)适度降低。DEET 不影响吡咯烷酮抑制的 hAChE 的脱羧酰化速度。总之，对人胆碱酯酶、DEET、吡咯烷酮、马拉氧磷和氯菊酯氧磷之间相互作用的体外研究表明，DEET 对 hAChE 和 hBChE 有较弱的抑制作用。测试的胆碱酯酶抑制剂的抑制效力未被 DEET 增强，并且它不影响吡咯烷酮抑制的 AChE 的再生速度。因此，本体外研究没有提供任何证据表明测试化合物对人胆碱酯酶具有协同作用。
