Acute effects of an insect repellent, N,N-diethyl-m-toluamide, on cholinesterase inhibition induced by pyridostigmine bromide in rats
Acute effects of an insect repellent, N,N-diethyl-m-toluamide, on cholinesterase inhibition induced by pyridostigmine bromide in rats
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DOI：
10.1006/taap.2000.8936
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发表时间：
2000-06-01
影响因子：
3.8
通讯作者：
Hume, AS
中科院分区：
文献类型：
--
作者：
Chaney, LA;Wineman, RW;Hume, AS
急性致死性相互作用之前已经描述了胆碱酯酶（ChE）抑制剂溴化吡啶斯的明（PB）和驱虫剂，N，N-二乙基-间甲苯酰胺（DEET）之间。这些药物之间的毒性相互作用机制尚不清楚。避蚊胺引起的膜渗透性改变可能促进或增强吸收，或改变外周限制性PB的分布，导致在给定剂量下ChE抑制增加。进行研究以调查在DEET存在下PB诱导的胆碱酯酶抑制。大鼠接受PB（1、2或3 mg/kg）、DEET（200 mg/kg）或PB + DEET的ip注射，剂量可增强急性致死性。胆碱酯酶活性测定在心脏，隔膜，血液，全脑，或特定的脑区使用改进的分光光度法。避蚊胺没有改变PB诱导的抑制胆碱酯酶活性在大鼠膈肌，心脏，或血液。单用避蚊胺对胆碱酯酶活性没有影响。PB单独不抑制全脑ChE，但PB（3 mg/kg）+ DEET（200 mg/kg）对全脑ChE活性产生显著抑制，约为对照组的60%。在特定的脑区，（皮质，小脑，髓质，下丘脑，海马，中脑，纹状体）PB单独不抑制胆碱酯酶活性。PB（3 mg/kg）+ DEET（200 mg/kg）使每个脑区的ChE活性降低至对照组的约65-75%，但这些结果在统计学上不显著。总之，避蚊胺并没有改变PB诱导的抑制胆碱酯酶活性的周边。虽然避蚊胺在高剂量下可能促进PB进入中枢神经系统，但令人怀疑的是，由此导致的胆碱酯酶活性的轻微降低是否会导致死亡。PB和DEET之间的致死性相互作用不太可能是通过胆碱能效应介导的，胆碱能效应是由胆碱酯酶抑制作用增加引起的。(C)北京大学出版社.
Acute lethal interactions have been previously described between a cholinesterase (ChE) inhibitor, pyridostigmine bromide (PB), and the insect repellent, N,N-diethyl-m-tolumaide (DEET). The mechanism of toxic interaction between these agents is unknown. Alterations in membrane permeability caused by DEET could facilitate or enhance absorption, or alter the distribution of peripherally restricted PB, causing increased inhibition of ChE at a given dose. Studies were conducted to investigate PB-induced ChE inhibition in the presence of DEET. Rats received ip injections of PB (1, 2, or 3 mg/kg), DEET (200 mg/kg), or PB + DEET at doses that potentiated acute lethality. ChE activity was measured in heart, diaphragm, blood, whole brain, or specific brain areas using a modified spectrophotometric assay. DEET did not alter PB-induced inhibition of ChE activity in rat diaphragm, heart, or blood. Administration of DEET alone had no effect on ChE activity. PB alone did not inhibit ChE in whole brain, but PB (3 mg/kg) + DEET (200 mg/kg) caused significant inhibition of whole brain ChE activity to approximately 60% of controls. In specific brain areas, (cortex, cerebellum, medulla, hypothalamus, hippocampus, midbrain, and striatum) PB alone did not inhibit ChE activity. PB (3 mg/kg) + DEET (200 mg/kg) reduced ChE activity to approximately 65-75% of controls in each brain area, but those results were not statistically significant. In conclusion, DEET did not alter PB-induced inhibition of ChE activity in the periphery. While DEET may have facilitated the access of PB into the CNS at high doses, it is doubtful that the resulting minor reduction in ChE activity would have resulted in death. It is unlikely that the lethal interaction between PB and DEET is mediated through a cholinergic effect resulting from increased inhibition of ChE. (C) 2000 Academic Press.