Todd Kathryn G, Baker Glen B
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Canada.
J Pharm Pharm Sci. 2008 May 16;11(2):14s-21s. doi: 10.18433/j34s38.
To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).
Male rats were administered PLZ (10 mg/kg) or VIG (1,000 mg/kg) i.p., and the rats were euthanized 4 hours later and the brains removed for analysis of levels of GABA and ALA (by electron capture gas chromatography after derivatization) and activities of MAO, GABA-T and ALA-T (radiochemical assays).
Both PLZ and VIG inhibited GABA-T and elevated GABA levels. Only PLZ inhibited MAO and ALA-T and elevated ALA levels. The effects of PLZ on both amino acids and their transaminases were blocked by pre-treatment with the MAO inhibitor tranylcypromine. This pretreament had no effect on the inhibition of GABA-T or the elevation of brain GABA levels produced by VIG.
At the doses studied, PLZ was as effective as VIG at elevating brain GABA levels, but, unlike VIG, also inhibited MAO and ALA-T (and increased brain ALA levels). Pretreatment of rats with the MAO inhibitor tranylcypromine prevented the increase in brain GABA and ALA levels with PLZ, but did not block the effect of VIG on GABA. These observations with tranylcypromine and PLZ support the hypothesis that an active metabolite of PLZ produced by the actions of MAO on this drug plays a major role in its GABA- and ALA-elevating actions.
比较苯乙肼（PLZ）和氨己烯酸（VIG）。苯乙肼是一种具有抗焦虑特性的抗抑郁药物，可抑制单胺氧化酶（MAO），同时还能提高大鼠脑内γ-氨基丁酸（GABA）和丙氨酸（ALA）的水平；氨己烯酸是一种抗惊厥药物，通过抑制GABA转氨酶（GABA-T）来提高脑内GABA水平。比较它们对脑内GABA和ALA水平以及MAO、GABA-T和ALA转氨酶（ALA-T）活性的影响。
给雄性大鼠腹腔注射PLZ（10毫克/千克）或VIG（1000毫克/千克），4小时后将大鼠安乐死并取出大脑，用于分析GABA和ALA的水平（衍生化后通过电子捕获气相色谱法）以及MAO、GABA-T和ALA-T的活性（放射化学分析）。
PLZ和VIG均抑制GABA-T并提高GABA水平。只有PLZ抑制MAO和ALA-T并提高ALA水平。PLZ对这两种氨基酸及其转氨酶的作用可被MAO抑制剂反苯环丙胺预处理所阻断。这种预处理对VIG抑制GABA-T或提高脑内GABA水平没有影响。
在所研究的剂量下，PLZ在提高脑内GABA水平方面与VIG一样有效，但与VIG不同的是，它还抑制MAO和ALA-T（并提高脑内ALA水平）。用MAO抑制剂反苯环丙胺预处理大鼠可防止PLZ使脑内GABA和ALA水平升高，但不阻断VIG对GABA的作用。反苯环丙胺和PLZ的这些观察结果支持以下假设：MAO对该药物作用产生的PLZ活性代谢物在其提高GABA和ALA水平的作用中起主要作用。
