Murphy D L, Karoum F, Pickar D, Cohen R M, Lipper S, Mellow A M, Tariot P N, Sunderland T
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA.
J Neural Transm Suppl. 1998;52:39-48. doi: 10.1007/978-3-7091-6499-0_5.
Marked, dose-dependent elevations in the urinary excretion of phenylethylamine, para-tyramine, and meta-tyramine were observed in depressed patients treated for three or more weeks with 10, 30, or 60 mg/day of the partially-selective inhibitor of MAO-B, selegiline (l-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90 mg/day for three or more weeks, produced elevations in these trace amines which were similar to those found with the highest dose of selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of 30 mg/day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect on MAO-A in humans in vivo) produced negligible changes in trace amine excretion. In comparison to recent studies of individuals lacking the genes for MAO-A, MAO-B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in individuals with a mutation affecting only MAO-A is in agreement with the observed lack of effect of clorgyline in the present study. Selegiline produced larger changes in trace amines--at least at the higher doses studied--than found in individuals lacking the gene for MAO-B, in agreement with other data suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in doses higher than 10 mg/day. Overall, trace amine elevations in individuals receiving the highest dose of deprenyl or receiving pargyline were approximately three to five-fold lower than the elevations observed in individuals lacking the genes for both MAO-A and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.
在接受10、30或60毫克/天的单胺氧化酶B（MAO-B）部分选择性抑制剂司来吉兰（左旋丙炔苯丙胺）治疗三周或更长时间的抑郁症患者中，观察到苯乙胺、对酪胺和间酪胺的尿排泄量有明显的剂量依赖性升高。在与其他结构相似的炔属MAO抑制剂进行的对比研究中，每天服用90毫克、持续三周或更长时间的MAO-B＞MAO-A抑制剂帕吉林，使这些痕量胺升高，与所研究的司来吉兰最高剂量产生的升高相似。每天服用30毫克、持续三周或更长时间的MAO-A选择性抑制剂氯吉兰（一种剂量/时间方案，此前报道可使尿、血浆和脑脊液中的3-甲氧基-4-羟基苯乙二醇（MHPG）降低＞80%，表明对人体体内的MAO-A有显著抑制作用），使痕量胺排泄的变化可忽略不计。与最近对缺乏MAO-A、MAO-B或同时缺乏MAO-A和MAO-B基因的个体的研究相比，仅影响MAO-A的突变个体中痕量胺排泄缺乏变化，与本研究中观察到的氯吉兰缺乏作用一致。司来吉兰在痕量胺方面产生的变化更大——至少在所研究的较高剂量下如此——比缺乏MAO-B基因的个体中观察到的变化大，这与其他数据一致，即当司来吉兰剂量高于10毫克/天时，对MAO-B抑制的选择性较低。总体而言，接受最高剂量丙炔苯丙胺或接受帕吉林的个体中痕量胺升高比同时缺乏MAO-A和MAO-B基因的个体中观察到的升高低约三至五倍，表明这些药物剂量对MAO-A和MAO-B的抑制不完全。
