Hallström G, Lindeke B, Khuthier A H, Al-Iraqi M A
Chem Biol Interact. 1981 Mar 1;34(2):185-200. doi: 10.1016/0009-2797(81)90130-7.
Pargyline undergoes metabolic N-oxidation in rat and rabbit liver microsomal preparations. The reaction requires oxygen and is NADPH dependent. N-oxidation and N-demethylation are equal in both control and induced rat liver microsomes, while N-oxidation is more dominant in rabbit tissue. Experiments investigating the CO-sensitivity and the effects of metyrapone suggest that cytochrome P-450 systems are involved in both reactions in the rat while an additional enzyme is responsible for the N-oxidation in the rabbit. Pargyline N-oxide is characterized by chemical instability and undergoes two consecutive rearrangements to yield propenal and Schiff bases, the latter undergoing hydrolysis to aldehydes and primary amines. Accordingly, due to the inherent instability of the N-oxide, metabolic N-oxidation of pargyline is, in addition to alpha-carbon oxidation, indicated as a metabolic route to benzaldehyde. Similarly the ease with which pargyline N-oxide generates propenal implicates N-oxidation as a metabolic route to be considered when evaluating the toxicity of pargyline.
在大鼠和兔肝微粒体制剂中，优降宁会发生代谢性N-氧化反应。该反应需要氧气且依赖于NADPH。在对照和诱导的大鼠肝微粒体中，N-氧化和N-去甲基化作用相当，而在兔组织中N-氧化作用更为显著。研究一氧化碳敏感性和甲吡酮作用的实验表明，细胞色素P-450系统参与大鼠的这两种反应，而兔体内的N-氧化反应由另一种酶负责。优降宁N-氧化物具有化学不稳定性，会经历两次连续重排生成丙烯醛和席夫碱，后者水解生成醛和伯胺。因此，由于N-氧化物固有的不稳定性，优降宁的代谢性N-氧化除了α-碳氧化外，还被认为是生成苯甲醛的一条代谢途径。同样，优降宁N-氧化物生成丙烯醛的容易程度表明，在评估优降宁的毒性时，N-氧化是一条需要考虑的代谢途径。
