Fries D S, de Vries J, Hazelhoff B, Horn A S
J Med Chem. 1986 Mar;29(3):424-7. doi: 10.1021/jm00153a019.
Six compounds having structural features in common with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and tested in mice for the ability to produce a prolonged decrease in nigrostriatal dopamine (DA) and DA metabolites. The compounds that were prepared and tested include the ester elimination products of the analgetic drugs alpha-prodine and trimeperidine. None of the compounds in this study, except for MPTP, produced significant neurotoxic effects in the mouse model. The study shows that minor changes in the tetrahydropyridine ring of MPTP result in a marked decrease in neurotoxicity.
合成了六种与1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）具有共同结构特征的化合物，并在小鼠中测试了它们使黑质纹状体多巴胺（DA）和DA代谢产物长期减少的能力。所制备和测试的化合物包括镇痛药α-丙哌啶和三甲哌啶的酯消除产物。在本研究中，除MPTP外，没有一种化合物在小鼠模型中产生明显的神经毒性作用。该研究表明，MPTP四氢吡啶环的微小变化会导致神经毒性显著降低。
