Department of Pharmacology and Environmental Toxicology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Madras-600 113, India.
Environ Toxicol Pharmacol. 1997 Jun 6;3(2):151-7. doi: 10.1016/s1382-6689(97)00009-4.
The organochlorine cyclodiene insecticide, endosulfan readily penetrates into the brain. The neurotoxic action of endosulfan has been attributed to its α-isomer. Endosulfan sulphate which is a chief metabolite of endosulfan seems to contribute to its acute neurotoxic action which is manifested by clonic convulsions in experimental animals. Convulsant and proconvulsant effects of endosulfan are apparent after its chronic exposure at low dose levels. These effects have been attributed to its γ-aminobutyric acid antagonistic action. Repeated exposure to low doses has resulted in behavioral changes too. Endosulfan-induced hyper-excitability has been associated with its muscarinic receptor stimulating action. The insecticide has been shown to produce aggressive behaviour and learning impairment by activating serotonergic mechanism. A dopaminergic involvement has been suggested for endosulfan-induced hypermotoractivity and circling movement. Animals exposed chronically to low doses of the insecticide have responded more markedly than control animals to the pharmacological actions of diazepam, chlorpromazine, pentobarbital and ethanol. The findings reviewed here emphasize awareness that chronic occupational exposure to low doses of endosulfan may result not only in behavioral abberations but in hazardous interaction with centrally acting drugs too.
有机氯环二烯类杀虫剂硫丹很容易穿透大脑。硫丹的神经毒性作用归因于其 α-异构体。硫丹硫酸盐是硫丹的主要代谢物，似乎对其急性神经毒性作用有贡献，这种作用表现为实验动物的阵挛性惊厥。在慢性低剂量暴露后，硫丹表现出明显的惊厥和促惊厥作用。这些作用归因于其γ-氨基丁酸拮抗作用。重复接触低剂量也会导致行为改变。硫丹诱导的过度兴奋与它的毒蕈碱受体刺激作用有关。这种杀虫剂通过激活血清素能机制产生攻击性行为和学习障碍。多巴胺能参与硫丹诱导的多动和转圈运动。与对照组动物相比，长期接触低剂量杀虫剂的动物对安定、氯丙嗪、戊巴比妥和乙醇的药理作用反应更为明显。这里综述的研究结果强调了这样一种认识，即慢性职业接触低剂量的硫丹不仅会导致行为异常，而且还会与中枢作用药物产生危险的相互作用。
