Johnson E A, Wu E Y, Rollema H, Booth R G, Trevor A J, Castagnoli N
Department of Pharmaceutical Chemistry, University of California, San Francisco.
Eur J Pharmacol. 1989 Jul 4;166(1):65-74. doi: 10.1016/0014-2999(89)90684-5.
The ability of various 1-methyl-4-phenylpyridinium (MPP+) analogs to inhibit the uptake of tritium labeled dopamine and MPP+ by synaptosomes prepared from neostriata of male C57 Black mice was measured and compared with their dopaminergic neurotoxic potential which was estimated by an in vivo intracerebral microdialysis technique. The correlation observed between these two properties suggests that nerve terminal uptake is an important step in the expression of the nigrostriatal toxicity of structural analogs of MPP+. The uptake inhibition and neurotoxic properties of this series of compounds appear to be highly structurally sensitive and suggest that few nitrogenous bases will be potent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-type neurotoxins.
测定了各种1-甲基-4-苯基吡啶鎓（MPP+）类似物对雄性C57黑小鼠新纹状体制备的突触体摄取氚标记多巴胺和MPP+的抑制能力，并将其与通过体内脑微透析技术估计的多巴胺能神经毒性潜力进行了比较。这两种特性之间观察到的相关性表明，神经末梢摄取是MPP+结构类似物黑质纹状体毒性表达中的一个重要步骤。该系列化合物的摄取抑制和神经毒性特性似乎对结构高度敏感，这表明很少有含氮碱会是有效的1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）型神经毒素。
