[用阿米替林、帕吉林和匹立吲哚抑制大鼠心脏和大脑中的单胺氧化酶A和B]

[Inhibition of monoamine oxidase A and B in the heart and brain of the rat with amitriptyline, pargyline and pirlindol].

作者信息

Schraven E, Reibert R

出版信息

Arzneimittelforschung. 1984;34(10):1258-60.

Abstract

The inhibition of monoamine oxidase (MAO) A and B by amitriptyline, pargyline and pirlindole was measured in heart and brain homogenates of rats with tryptamine and beta-phenylethylamine as substrates. The tricyclic antidepressant amitriptyline inhibited MAO B stronger in the brain (Ki = 8.41 X 10(-6) mol/l) as well as in the heart (Ki = 7.03 X 10(-5) mol/l) compared to the A-form (1.51 X 10(-4) and 1.03 X 10(-4) mol/l, respectively). Pargyline diminished the activity of both enzyme forms of the heart in the same range (4.29 and 1.60 X 10(-6) mol/l), whereas in the brain the B-form was blocked in a more pronounced manner, too (5.80 X 10(-8) and 4.01 X 10(-6) mol/l, respectively). In contrast to amitriptyline and pargyline pirlindole inhibited the MAO with tryptamine as a substrate in the brain 100 times (2.49 X 10(-7) mol/l) and in the heart nearly 1000 times (3.42 X 10(-8) mol/l) more than with phenylethylamine as a substrate (5.21 and 5.99 X 10(-5) mol/l, respectively). These results show that amitriptyline and pargyline are relatively selective inhibitors of MAO B, whereas pirlindole blocks the A-form of MAO much stronger than MAO B.

摘要

以色胺和β-苯乙胺为底物，在大鼠心脏和脑匀浆中测定了阿米替林、帕吉林和匹克隆朵对单胺氧化酶（MAO）A和B的抑制作用。与MAO A（分别为1.51×10⁻⁴和1.03×10⁻⁴mol/L）相比，三环类抗抑郁药阿米替林在脑中（Ki = 8.41×10⁻⁶mol/L）和心脏中（Ki = 7.03×10⁻⁵mol/L）对MAO B的抑制作用更强。帕吉林在相同范围内降低了心脏中两种酶形式的活性（4.29和1.60×10⁻⁶mol/L），而在脑中，MAO B形式也受到更显著的阻断（分别为5.80×10⁻⁸和4.01×10⁻⁶mol/L）。与阿米替林和帕吉林不同，匹克隆朵以色胺为底物时对脑中MAO的抑制作用比对苯乙胺为底物时强100倍（2.49×10⁻⁷mol/L），在心脏中则强近1000倍（3.42×10⁻⁸mol/L）（分别为5.21和5.99×10⁻⁵mol/L）。这些结果表明，阿米替林和帕吉林是相对选择性的MAO B抑制剂，而匹克隆朵对MAO A形式的阻断作用比对MAO B强得多。