ANALOGS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AS MONOAMINE-OXIDASE SUBSTRATES - A 2ND RING IS NOT NECESSARY
ANALOGS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AS MONOAMINE-OXIDASE SUBSTRATES - A 2ND RING IS NOT NECESSARY
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DOI：
10.1016/0304-3940(87)90422-8
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发表时间：
1987-05-19
影响因子：
2.5
通讯作者：
MARSDEN, CD
中科院分区：
文献类型：
--
作者：
GIBB, C;WILLOUGHBY, J;MARSDEN, CD
1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）被单胺氧化酶B （MAO B）氧化为神经毒性代谢物。使用两种比色测定法，我们检查了其结构类似物的范围，作为该酶的进一步底物，以确定可能也具有神经毒性的环境或内源性化合物的类型。吡啶环完全饱和或不饱和的化合物不是底物；四氢基- β的范围也没有。-碳啉或异喹啉。发现了4种MAO底物：1-甲基-4-（2”-甲基苯基）-1,2,3,6-四氢吡啶（2”-me - mptp）， 4-苯基-1,2,3,6-四氢吡啶（PTP）， 4-（对氯苯基）-1,2,3,6-四氢吡啶（Cl-PTP）和1-甲基-1,2,3,6-四氢吡啶-羧酸乙酯（乙基- mtp -羧酸乙酯）。羧酸乙酯是特别有趣的，因为它表明没有苯基环的四氢吡啶也可以作为底物。Cl-PTP、PTP和乙基- mtp -羧酸酯似乎部分被MAO a代谢，2”-Me-MPTP氧化的抑制敏感性更为复杂。
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is oxidized to a neurotoxic metabolite by monoamine oxidase B (MAO B). Using two colorimetric assays, we have examined a range of its structural analogues as possible further substrates of this enzyme in order to identify the types of environmental or endogenous compounds that might also be neurototoxic. Compounds with fully saturated or unsaturated of pyridine ring were not substrates; nor were a range of tetrahdyro-.beta.-carbolines or isoquinolines. Four substrates for MAO were found, 1-methyl-4-(2''-methylphenyl)-1,2,3,6-tetrahydropyridine (2''-Me-MPTP), 4-phenyl-1,2,3,6-tetrahydropyridine (PTP), 4-(p-chlorophenyl)-1,2,3,6-tetrahydropyridine (Cl-PTP) and ethyl-1-methyl-1,2,3,6-tetrahydro-4-pyridine-carboxylate (ethyl-MTP-carboxylate). Ethyl-MTP-carboxylate is of particular interest as it shows that a tetrahydropyridine without a phenyl ring can also be a substrate. Cl-PTP, PTP and ethyl-MTP-carboxylate appeared to be partially metabolised by MAO A. The inhibitory sensitivity of 2''-Me-MPTP oxidation was more complex.