Youdim M B
Br J Pharmacol. 1983 Jun;79(2):477-80. doi: 10.1111/j.1476-5381.1983.tb11021.x.
In vivo clorgyline (5 mg/kg) and (-)-deprenyl (5 mg/kg) selectively inhibit monoamine oxidase (MAO) type A and B activities in rat brain hypothalamus and caudate nucleus using 5-hydroxytryptamine (5-HT), noradrenaline (NA), and beta-phenylethylamine (PEA) as substrates. Clorgyline induces a significant increase in NA concentrations of hypothalamus and caudate nucleus; however (-)-deprenyl is without effect. The combination of clorgyline and (-)-deprenyl at the above doses completely inhibits both forms of MAO, resulting in an even greater increase in NA levels in both brain areas than observed with clorgyline. The non-selective inhibitor tranylcypromine (5 mg/kg) produced a similar effect. Rats pretreated with the selective or the non-selective inhibitors but given L-DOPA (50 mg/kg) have a similar pattern of brain NA, but its concentrations are higher in both brain regions. The results indicate that although in vitro NA may be an exclusive substrate for MAO type A, in vivo, when this enzyme form is selectively inhibited, NA at high concentrations can be a substrate for MAO type B.
体内,使用5-羟色胺(5-HT)、去甲肾上腺素(NA)和β-苯乙胺(PEA)作为底物,氯吉兰(5毫克/千克)和(-)-司来吉兰(5毫克/千克)可选择性抑制大鼠脑下丘脑和尾状核中的单胺氧化酶(MAO)A型和B型活性。氯吉兰可使下丘脑和尾状核中的NA浓度显著升高;然而,(-)-司来吉兰则无此作用。上述剂量的氯吉兰和(-)-司来吉兰联合使用可完全抑制两种形式的MAO,导致两个脑区的NA水平升高幅度甚至比单独使用氯吉兰时更大。非选择性抑制剂反苯环丙胺(5毫克/千克)产生了类似的效果。用选择性或非选择性抑制剂预处理但给予左旋多巴(50毫克/千克)的大鼠,其脑内NA的模式相似,但其在两个脑区的浓度均较高。结果表明,尽管在体外NA可能是MAO A型的唯一底物,但在体内,当这种酶形式被选择性抑制时,高浓度的NA可以成为MAO B型的底物。