Phentermine inhibition of recombinant human liver monoamine oxidases A and B.
Phentermine inhibition of recombinant human liver monoamine oxidases A and B.
复制标题
芬特明对重组人肝单胺氧化酶 A 和 B 的抑制作用。
DOI：
10.1016/s0006-2952(02)00840-7
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发表时间：
2002
影响因子：
5.8
通讯作者：
Edmondson,DaleE
中科院分区：
文献类型：
--
作者：
Nandigama,RaviK;Newton-Vinson,Paige;Edmondson,DaleE
最近对大鼠组织制备物的研究表明，厌食药物芬特明通过抑制单胺氧化酶（MAO）A抑制5-羟色胺降解，KI值为85-88μM，其效力与其他可逆性MAO抑制剂相似（Ulus等人，Biochem Pharmacol 2000;59：1611-21）。由于已知大鼠和人之间在MAO的底物和抑制剂特异性方面存在差异，因此测定了芬特明与重组人纯化的MAO A和MAO B制剂的相互作用。芬特明竞争性抑制人MAO A，KI值为498±60μM，比大鼠酶的KI值弱约6倍。还观察到芬特明是重组人肝MAO B的竞争性抑制剂，KI值为375±42μM，与大鼠酶（310-416μM）观察到的值相似。与大鼠组织制剂的行为相反，未观察到纯化的可溶性人MAO制剂的芬特明抑制的缓慢时间依赖性行为。差分吸收光谱研究表明，人MAO A和MAO B的共价FAD部分的扰动相似，这表明两种酶的结合模式相似。这些数据表明芬特明对人MAO A（或MAO B）的抑制太弱而不具有药理学相关性。
Recent studies with rat tissue preparations have suggested that the anorectic drug phentermine inhibits serotonin degradation by inhibition of monoamine oxidase (MAO) A with a KIvalue of 85–88μM, a potency suggested to be similar to that of other reversible MAO inhibitors (Ulus et al., Biochem Pharmacol 2000;59:1611–21). Since there are known differences between rats and humans in substrate and inhibitor specificities of MAOs, the interactions of phentermine with recombinant human purified preparations of MAO A and MAO B were determined. Human MAO A was competitively inhibited by phentermine with a KIvalue of 498±60μM, a value approximately 6-fold weaker than that observed for the rat enzyme. Phentermine was also observed to be a competitive inhibitor of recombinant human liver MAO B with a KIvalue of 375±42μM, a value similar to that observed with the rat enzyme (310–416μM). In contrast to the behavior with rat tissue preparations, no slow time-dependent behavior was observed for phentermine inhibition of purified soluble human MAO preparations. Difference absorption spectral studies showed similar perturbations of the covalent FAD moieties of both human MAO A and MAO B, which suggests a similar mode of binding in both enzymes. These data suggest that phentermine inhibition of human MAO A (or of MAO B) is too weak to be of pharmacological relevance.
厌食药物的中枢机制
影响因子：
4.9
作者：
R. Samanin
通讯作者：
R. Samanin
酿酒酵母中表达的人肝脏催化活性 A 型单胺氧化酶含有共价 FAD。
DOI：
--
发表时间：
1990
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
W. Weyler;C. C. Titlow;J. Salach
通讯作者：
J. Salach
影响因子：
2.9
作者：
Miller, JR;Edmondson, DE
通讯作者：
Edmondson, DE