Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease.

E H Heinonen, M Savijärvi, M Kotila, A Hajba, M Scheinin
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引用次数: 21

Abstract

A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Bråne-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4-dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline.

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selegiline抑制单胺氧化酶对阿尔茨海默病患者脑脊液去甲肾上腺素和单胺代谢物浓度的影响
对12例阿尔茨海默病(AD)患者进行了双盲交叉试验,主要是为了检验该设计在研究塞来吉兰(10mg /d)治疗AD的临床效果中的适用性。在基线和四周治疗期(安慰剂和斯来吉兰)结束时收集脑脊液(CSF)样本,用于测定去甲肾上腺素(NA)和几种单胺代谢物的浓度。使用Ferm's和gottfries - br ne- steen (GBS)痴呆量表评估痴呆的严重程度。多巴胺代谢物3,4-二羟基苯基乙酸(DOPAC)和NA代谢物3,4-二羟基苯基乙二醇(DHPG)和3-甲氧基-4-羟基苯基乙二醇(MHPG)浓度在selegiline治疗期间显著降低。selegiline处理期间,高香草酸(HVA)浓度有明显降低的趋势,而NA、5-羟基吲哚乙酸(5-HIAA)和色氨酸的浓度差异不显著。该研究设计不适合分析临床结果,因为两个量表都存在显著的结转效应。由于只能使用第一期数据进行分析,因此Ferm's或GBS量表的得分没有显着差异,但可以发现明显的有利于selegiline的积极趋势。
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