米拉美胺对大鼠额叶皮质中多巴胺和5-羟色胺细胞外及组织浓度的影响。
Effect of milacemide on extracellular and tissue concentrations of dopamine and 5-hydroxytryptamine in rat frontal cortex.
作者信息
Semba J, Doheny M, Patsalos P N, Sarna G, Curzon G
机构信息
University Department of Clinical Neurology, Institute of Neurology, Queen Square, London.
出版信息
Br J Pharmacol. 1992 Jan;105(1):59-62. doi: 10.1111/j.1476-5381.1992.tb14210.x.
Abstract
- Milacemide is a glycine prodrug which is both an inhibitor and a substrate for monoamine oxidase-type B (MAO-B) and also an inhibitor of MAO-type A (MAO-A). Its effects on dopamine and 5-hydroxytryptamine (5-HT) metabolism in rat frontal cortex tissue and dialysate were evaluated. 2. Dialysate dopamine concentrations increased linearly and dose-dependently after milacemide administration (100, 200, 400 mg kg-1, i.p.), peaking at 1 h. A concomitant dose-dependent decrease in dialysate 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations was observed but these changes were smaller (27% and 40% respectively) than the change in dopamine (125% after 400 mg kg-1 milacemide). 3. Dialysate 5-HT was significantly increased only at 1.5 h after giving milacemide 400 mg kg-1. Dialysate 5-hydroxyindoleacetic acid (5-HIAA) concentration was not affected. 4. Milacemide (400 mg kg-1) at 1.5 h post-administration significantly increased frontal cortex tissue concentrations of dopamine and 5-HT; the percentage increase in dopamine being about four times that of 5-HT. Metabolite concentrations, including 5-HIAA, decreased. Changes in tissue and dialysate dopamine, DOPAC and HVA were approximately proportionate to each other. 5. The results are explicable in terms of an inhibition by milacemide of MAO-A.
摘要
- 米拉美胺是一种甘氨酸前体药物，它既是单胺氧化酶B型（MAO - B）的抑制剂和底物，也是单胺氧化酶A型（MAO - A）的抑制剂。评估了其对大鼠额叶皮质组织和透析液中多巴胺及5 - 羟色胺（5 - HT）代谢的影响。2. 腹腔注射米拉美胺（100、200、400 mg kg⁻¹）后，透析液中多巴胺浓度呈线性且剂量依赖性增加，在1小时达到峰值。同时观察到透析液中3,4 - 二羟基苯乙酸（DOPAC）和高香草酸（HVA）浓度呈剂量依赖性降低，但这些变化比多巴胺的变化小（分别为27%和40%），而400 mg kg⁻¹米拉美胺后多巴胺变化为125%。3. 仅在给予400 mg kg⁻¹米拉美胺后1.5小时，透析液中5 - HT显著增加。透析液中5 - 羟吲哚乙酸（5 - HIAA）浓度未受影响。4. 给药后1.5小时，米拉美胺（400 mg kg⁻¹）显著增加额叶皮质组织中多巴胺和5 - HT的浓度；多巴胺增加的百分比约为5 - HT的四倍。包括5 - HIAA在内的代谢物浓度降低。组织和透析液中多巴胺、DOPAC和HVA的变化大致成比例。5. 这些结果可用米拉美胺对MAO - A的抑制作用来解释。
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