Hoag M K, Schmidt-Peetz M, Lampen P, Trevor A, Castagnoli N
Division of Toxicology, University of California School of Pharmacy, San Francisco 94143-0446.
Chem Res Toxicol. 1988 Mar-Apr;1(2):128-31. doi: 10.1021/tx00002a007.
Studies on the metabolic bioactivation of the psychotomimetic amine phencyclidine have been pursued through the characterization of a new metabolite which is formed via initial cytochrome P-450 catalyzed oxidation of the parent drug to the corresponding iminium species. CI mass spectrometric and diode array UV and 1H NMR spectral analyses provided evidence for the conjugated amino enone compound, 1-(1-phenylcyclohexyl)-2,3-dihydro-4-pyridone. Confirmation of the proposed structure was achieved by comparing the 1H NMR and high-resolution EI mass spectral properties of the metabolic isolate with the corresponding spectra of an authentic synthetic sample. Possible intermediates involved in the formation of the dihydropyridone metabolite from the phencyclidine iminium ion are discussed in terms of structural analogies to reactive intermediates formed in the bioactivation of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
关于拟精神病胺苯环利定代谢生物活化的研究，是通过对一种新代谢物的表征来进行的，该代谢物是由母体药物最初经细胞色素P - 450催化氧化为相应的亚胺离子而形成的。CI质谱、二极管阵列紫外光谱和1H NMR光谱分析为共轭氨基烯酮化合物1-(1-苯基环己基)-2,3-二氢-4-吡啶酮提供了证据。通过将代谢分离物的1H NMR和高分辨率EI质谱特性与真实合成样品的相应光谱进行比较，证实了所提出的结构。根据与黑质纹状体毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）生物活化过程中形成的反应中间体的结构类比，讨论了从苯环利定亚胺离子形成二氢吡啶酮代谢物可能涉及的中间体。
