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首页> 外文OA文献 >Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in β-phenylethylamine
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Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in β-phenylethylamine

机译：与MAO-A抑制剂和MAO-B抑制剂联合治疗可通过增加β-苯乙胺使细胞外去甲肾上腺素水平比单独的MAO-A抑制剂高

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Monoamine oxidase inhibitors (MAO inhibitors) have been widely used as antidepressants. However, it remains unclear whether a difference exists between non-selective MAO inhibitors and selective MAO-A inhibitors in terms of their antidepressant effects. Using in vivo microdialysis methods, we measured extracellular noradrenaline and serotonin levels following administration of Ro 41-1049, a reversible MAO-A inhibitor and/or lazabemide, a reversible MAO-B inhibitor in the medial prefrontal cortex (mPFC) of rats. We examined the effect of local infusion of β-phenylethylamine to the mPFC of rats on extracellular noradrenaline and serotonin levels. Furthermore, the concentrations of β-phenylethylamine in the tissue of the mPFC after combined treatment with Ro 41-1049 and lazabemide were measured. The Ro 41-1049 alone and the combined treatment significantly increased extracellular noradrenaline levels compared with vehicle and lazabemide alone. Furthermore, the combined treatment increased noradrenaline levels significantly more than Ro 41-1049 alone did. The Ro 41-1049 alone and the combined treatment significantly increased extracellular serotonin levels compared with vehicle and lazabemide alone, but no difference in serotonin levels was found between the combined treatment group and the Ro 41-1049 group. Local infusion of low-dose β-phenylethylamine increased extracellular noradrenaline levels, but not that of serotonin. Only the combined treatment significantly increased β-phenylethylamine levels in tissues of the mPFC. Our results suggest that the combined treatment with a MAO-A inhibitor and a MAO-B inhibitor strengthens antidepressant effects because the combined treatment increases extracellular noradrenaline levels more than a MAO-A inhibitor alone through increases in β-phenylethylamine.
机译：单胺氧化酶抑制剂（MAO抑制剂）已被广泛用作抗抑郁药。但是，就抗抑郁作用而言，尚不清楚非选择性MAO抑制剂和选择性MAO-A抑制剂之间是否存在差异。使用体内微透析方法，我们在大鼠内侧前额叶皮层（mPFC）中施用Ro 41-1049（一种可逆的MAO-A抑制剂）和/或lazabemide（一种可逆的MAO-B抑制剂）后，测量了细胞外去甲肾上腺素和血清素的水平。我们研究了向大鼠mPFC局部输注β-苯乙胺对细胞外去甲肾上腺素和血清素水平的影响。此外，测定了在用Ro 41-1049和拉沙贝米联合治疗后的mPFC组织中β-苯乙胺的浓度。与单独的赋形剂和拉扎贝胺相比，单独的Ro 41-1049和联合治疗显着增加了细胞外去甲肾上腺素的水平。此外，联合治疗比单独的Ro 41-1049显着增加去甲肾上腺素水平。与单独的赋形剂和拉扎比胺相比，单独的Ro 41-1049和联合治疗显着增加了细胞外血清素水平，但在联合治疗组和Ro 41-1049组之间未发现血清素水平有差异。局部输注小剂量β-苯乙胺可增加细胞外去甲肾上腺素水平，但不会增加5-羟色胺水平。仅联合治疗显着增加了mPFC组织中的β-苯乙胺水平。我们的结果表明，与MAO-A抑制剂和MAO-B抑制剂联合使用可增强抗抑郁作用，因为与单独使用MAO-A抑制剂相比，通过增加β-苯乙胺，联合使用可以增加细胞外去甲肾上腺素水平。

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