Befloxatone，一种新型的可逆和选择性单胺氧化酶-A抑制剂。一，生化概况。,Journal of Pharmacology and Experimental Therapeutics

当前位置： X-MOL 学术 › J. Pharmacol. Exp. Ther. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Befloxatone，一种新型的可逆和选择性单胺氧化酶-A抑制剂。一，生化概况。
Journal of Pharmacology and Experimental Therapeutics ( IF 3.1 ) Pub Date : 1996-04-01 , DOI: 10.1163/2211730x96x00144
O Curet ₁ , G Damoiseau , N Aubin , N Sontag , V Rovei , F X Jarreau

Affiliation

新型的恶唑烷酮衍生物Befloxatone可选择性和竞争性抑制人和大鼠脑，心脏，肝脏和十二指肠匀浆中的单胺氧化酶（MAO）-A，MAO-A的Ki值范围为1.9至3.6 nM，MAO-A的Ki值范围为270至900 nM。 MAO-B。在体外，倍氟沙酮在抑制MAO-A活性方面比参考化合物更有效（倍氟沙酮> harmaline>溴发烟碱> BW 137OU87> RS 8359>托洛沙酮>氯倍比胺）。氟虫酮对MAO-A的抑制作用是时间依赖性的，稀释后可完全逆转。口服给予后，倍氟沙酮离体诱导大鼠离体大脑和十二指肠MAO-A活性的剂量依赖性和选择性抑制，ED50值分别为0.06和0.025 mg / kg。在两种组织中，befloxatone（0.5 mg / kg po）均降低MAO-B活性仅20％。在大脑里在肝和十二指肠中，倍氟沙酮对MAO-A活性的抑制作用持续时间很短。服用倍氟沙酮（口服0.75 mg / kg）后二十四小时，大脑中MAO-A活性完全恢复，但十二指肠和肝脏中的酶活性仍分别降低了38％和56％。在大鼠大脑中，贝沙酮（0.75 mg / kg口服）增加去甲肾上腺素，多巴胺和5-羟色胺的水平，并降低其各自脱氨基代谢产物的水平。这些变化是剂量依赖性的，并且在给药后24小时逆转。此外，befloxatone（0.75 mg / kg po）降低大脑和血浆中的游离3,4-二羟基苯基乙二醇含量。Befloxatone（10 microM）不会改变二胺或苄基胺氧化酶的活性，并且不会与单胺摄取机制或各种神经递质或药物受体位点相互作用。总之，贝氟沙酮的神经化学特征表明该化合物是一种选择性，竞争性，有效和可逆的MAO-A抑制剂。

"点击查看英文标题和摘要"

Befloxatone, a new reversible and selective monoamine oxidase-A inhibitor. I. Biochemical profile.

Befloxatone, a novel oxazolidinone derivative, inhibited selectively and competitively monoamine oxidase (MAO)-A in human and rat brain, heart, liver and duodenum homogenates with Ki values ranging from 1.9 to 3.6 nM for MAO-A and from 270 to 900 nM for MAO-B. In vitro, befloxatone was more potent at inhibiting MAO-A activity than reference compounds (befloxatone > harmaline > brofaromine > BW 137OU87 > RS 8359 > toloxatone > moclobemide). The inhibition of MAO-A by befloxatone was time-dependent and fully reversible after dilution. After p.o. administration, befloxatone induced a dose-dependent and selective inhibition of rat brain and duodenum MAO-A activities ex vivo with ED50 values of 0.06 and 0.025 mg/kg, respectively. Befloxatone (0.5 mg/kg p.o.) decreased MAO-B activity by only 20% in both tissues. In the brain, liver and duodenum, the inhibition of MAO-A activity by befloxatone was short lasting. Twenty-four hours after administration of befloxatone (0.75 mg/kg p.o.), a full recovery of MAO-A activity was observed in the brain, but the enzyme activity was still decreased by 38 and 56% in the duodenum and liver, respectively. In the rat brain, befloxatone (0.75 mg/kg p.o.) increased levels of norepinephrine, dopamine and 5-hydroxytryptamine and decreased levels of their respective deaminated metabolites. These variations were dose-dependent and reversed 24 hr after administration. In addition, befloxatone (0.75 mg/kg p.o.) decreased free 3,4-dihydroxyphenylethylene glycol levels in the brain and plasma. Befloxatone (10 microM) did not modify the activities of diamine or benzylamine oxidase and did not interact with monoamine uptake mechanisms or with a variety of neurotransmitter or drug receptor sites. In conclusion, the neurochemical profile of befloxatone demonstrates that this compound is a selective, competitive, potent and reversible MAO-A inhibitor.

更新日期：2019-11-01

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南