Hadjiconstantinou M, Hubble J P, Wemlinger T A, Neff N H
Department of Psychiatry, Ohio State University, College of Medicine, Columbus.
J Pharmacol Exp Ther. 1994 Aug;270(2):639-44.
Administration of the irreversible cholinesterase inhibitor isoflurophate (diisopropylfluorophosphate, DFP) before 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) enhanced the loss in tyrosine hydroxylase activity and dopamine and 3,4-dihydroxy-phenylacetic acid content in the striatum of mice in a dose-dependent manner. The effect of DFP on the MPTP-induced changes of dopaminergic markers was evident 30 days after initiating treatment, suggesting augmented neurotoxicity. Neurotoxicity was also enhanced by prior treatment with nicotine, carbachol or oxotremorine. We conclude that activation of either muscarinic or nicotinic receptors enhances the neurotoxicity of MPTP.
在给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）之前给予不可逆性胆碱酯酶抑制剂异氟磷（二异丙基氟磷酸酯，DFP），会以剂量依赖的方式增强小鼠纹状体中酪氨酸羟化酶活性以及多巴胺和3,4-二羟基苯乙酸含量的损失。DFP对MPTP诱导的多巴胺能标志物变化的影响在开始治疗30天后很明显，表明神经毒性增强。预先用尼古丁、卡巴胆碱或氧化震颤素治疗也会增强神经毒性。我们得出结论，毒蕈碱受体或烟碱受体的激活都会增强MPTP的神经毒性。
