Pickar D, Cohen R M, Jimerson D C, Lake C R, Murphy D L
Psychopharmacology (Berl). 1981;74(1):8-12. doi: 10.1007/BF00431748.
The relationship between changes in IV tyramine pressor sensitivity accompanying selective monoamine oxidase (MAO) inhibitor treatment and estimates of MAO-A and MAO-B inhibition in vivo were studied. Reductions in platelet MAO activity provided an index of MAO-B inhibition, while changes in plasma 3-methoxy-4-hydroxyphenethylene glycol (MHPG) were used as an hypothesized reflection of MAO-A inhibition. Chronic treatment with the MAO-A inhibitor clorgyline and the MAO-B inhibitor pargyline showed significant inhibition of the alternate MAO enzyme as well, although this crossover effect was greater for pargyline than clorgyline. The MAO-B inhibitor deprenyl appeared to maintain the greatest degree of MAO inhibition selectivity in vivo. Tyramine pressor sensitivity changes accompanying administration of the MAO inhibitors were highly correlated with decreases in plasma MHPG (r = 0.92), supporting our previous data indicating the rank order of clorgyline greater than pargyline greater than deprenyl for enhancement of tyramine pressor sensitivity and, thus, suggesting that tyramine potentiation is primarily a function of MAO-A rather than MAO-B inhibition. Changes in plasma MHPG are suggested to provide a potentially useful clinical index of in vivo MAO-A inhibition.
研究了选择性单胺氧化酶(MAO)抑制剂治疗过程中静脉注射酪胺升压敏感性的变化与体内MAO-A和MAO-B抑制作用评估之间的关系。血小板MAO活性的降低提供了MAO-B抑制作用的指标,而血浆3-甲氧基-4-羟基苯乙二醇(MHPG)的变化被用作MAO-A抑制作用的假定反映。MAO-A抑制剂氯吉兰和MAO-B抑制剂帕吉林的长期治疗也显示出对另一种MAO酶有显著抑制作用,尽管这种交叉效应帕吉林比氯吉兰更明显。MAO-B抑制剂司来吉兰在体内似乎保持了最大程度的MAO抑制选择性。MAO抑制剂给药后酪胺升压敏感性的变化与血浆MHPG的降低高度相关(r = 0.92),支持了我们之前的数据,即氯吉兰增强酪胺升压敏感性的作用大于帕吉林大于司来吉兰,因此表明酪胺增强作用主要是MAO-A而非MAO-B抑制的作用。血浆MHPG的变化被认为可提供体内MAO-A抑制作用的潜在有用临床指标。