MDL 72,974：一种强效且选择性的单胺氧化酶B型酶激活不可逆抑制剂，具有用于帕金森病的潜力。

MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease.

作者信息

Zreika M, Fozard J R, Dudley M W, Bey P, McDonald I A, Palfreyman M G

机构信息

Merrell Dow Research Institute, Strasbourg, France.

出版信息

J Neural Transm Park Dis Dement Sect. 1989;1(4):243-54. doi: 10.1007/BF02263478.

DOI:10.1007/BF02263478

PMID:2597310

Abstract

MDL 72,974, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, was designed to be a selective inhibitor of monoamine oxidase type B (MAO-B). In vitro, the compound inhibits rat brain mitochondrial MAO in a concentration and time-dependent fashion and shows marked selectivity for the B form (IC50 = 680 and 3.6 nM for MAO-A and MAO-B, respectively). After oral administration to rats, the compound shows preferential inhibition of brain MAO-B with ED50 values of 8 and 0.18 mg/kg p.o. for the A and B forms, respectively. Selectivity is retained on repeat dosing. MDL 72,974 did not significantly potentiate the cardiovascular effects of intraduodenually-administered tyramine in anaesthetized rats and had only minor indirect sympathomimatic effects in the pithed rat. At MAO-B selective doses the neurotoxic effect of MPTP in mice was blocked.

摘要

MDL 72,974，即(E)-2-(4-氟苯乙基)-3-氟烯丙胺，被设计为单胺氧化酶B型（MAO-B）的选择性抑制剂。在体外，该化合物以浓度和时间依赖性方式抑制大鼠脑线粒体MAO，并对B型表现出显著的选择性（MAO-A和MAO-B的IC50分别为680和3.6 nM）。给大鼠口服该化合物后，对脑MAO-B表现出优先抑制作用，A和B型的口服ED50值分别为8和0.18 mg/kg。重复给药时仍保持选择性。MDL 72,974不会显著增强麻醉大鼠十二指肠内注射酪胺对心血管系统的影响，对脊髓麻醉大鼠仅有轻微的间接拟交感神经作用。在MAO-B选择性剂量下，可阻断MPTP对小鼠的神经毒性作用。