Lloyd K G, Davidson L, Hornykiewicz O
J Pharmacol Exp Ther. 1975 Dec;195(3):453-64.
Post-mortem brain material from control and Parkinson's disease patients was examined to elucidate further the neurochemistry of this disease and to determine the mechanism of action of L-dopa as a therapeutic agent. The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined. In the non-dopa-treated Parkinsonian patients, the greatest decreases were detected for striatal DA and dopa D, with homovanillic acid and tyrosine hydroxylase levels showing a lesser change. The activities of monoamine oxidase and catechol-O-methyl transferase in the striatal nuclei were not different from the controls. The putamen was consistently the most severely affected region. Dopa and 3-O-methyldopa were detectable in all brain areas only in those patients treated with L-dopa shortly before death. The mean concentrations of DA in the striatum of these patients were 1) 9 to 15 times higher than those in non-dopa-treated patients, 2) related to the time before death of the last dose of L-dopa and 3) greater in the striatum of patients clinically classified as "good responders" as compared to "poor responders." Although L-dopa therapy increased homovanillic acid levels in all brain areas, a preferential increase was observed in the striatum. It was concluded that L-dopa's principal therapeutic effects in Parkinson's disease are consistent with its transformation to DA in the striatum.
对来自对照组和帕金森病患者的尸检脑材料进行了检查，以进一步阐明该疾病的神经化学，并确定左旋多巴作为治疗药物的作用机制。检测了L-芳香族氨基酸脱羧酶（多巴脱羧酶）、酪氨酸羟化酶、单胺氧化酶和儿茶酚-O-甲基转移酶的活性；此外，还测定了多巴、3-O-甲基多巴、多巴胺（DA）和高香草酸（HVA）的组织水平。在未接受多巴治疗的帕金森病患者中，纹状体DA和多巴脱羧酶的下降最为明显，高香草酸和酪氨酸羟化酶水平的变化较小。纹状体核中单胺氧化酶和儿茶酚-O-甲基转移酶的活性与对照组无差异。壳核始终是受影响最严重的区域。仅在那些在死亡前不久接受左旋多巴治疗的患者的所有脑区中可检测到多巴和3-O-甲基多巴。这些患者纹状体中DA的平均浓度为：1）比未接受多巴治疗的患者高9至15倍；2）与最后一剂左旋多巴给药至死亡的时间有关；3）临床分类为“良好反应者”的患者纹状体中的DA浓度高于“不良反应者”。尽管左旋多巴治疗使所有脑区的高香草酸水平升高，但纹状体中观察到优先升高。得出的结论是，左旋多巴在帕金森病中的主要治疗作用与其在纹状体中转化为DA一致。
