抗抑郁药匹吲哚及其脱氢衍生物对单胺氧化酶-A活性和γ-氨基丁酸A型受体的影响。
Effects of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase-A and on GABAA receptors.
作者信息
Medvedev A E, Shvedov V I, Chulkova T M, Fedotova O A, Saederup E, Squires R F
机构信息
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia.
出版信息
Neurochem Res. 1996 Dec;21(12):1521-6. doi: 10.1007/BF02533100.
The effects of pirlindole and dehydro-pirlindole on GABAA receptors and MAO-A activity were investigated in vitro. Pirlindole was inactive as a GABA antagonist. Dehydro-pirlindole exhibited partial and selective blockade of a subset of GABAA receptors with an EC50 of 12 microM and maximum reversal (delta Bopt) of 42%. Inhibition of rat brain and human placenta MAO-A by both compounds was much more potent (with IC50 range 0.3-0.005 microM). Their effects on MAO-A activity were partially reversible in vitro. In contrast to pirlindole, dehydro-pirlindole may act not only as MAO-A inhibitor but also as a clozapine-like selective GABAA receptor blocker, preferentially blocking a subset of GABAA receptors that are not sensitive to DMCM or Ro 5-4864.
在体外研究了匹吲哚和脱氢匹吲哚对GABAA受体及单胺氧化酶A（MAO-A）活性的影响。匹吲哚作为GABA拮抗剂无活性。脱氢匹吲哚对一部分GABAA受体表现出部分性和选择性阻断作用，其半数有效浓度（EC50）为12微摩尔，最大翻转率（δBopt）为42%。这两种化合物对大鼠脑和人胎盘MAO-A的抑制作用更强（半数抑制浓度（IC50）范围为0.3 - 0.005微摩尔）。它们对MAO-A活性的影响在体外部分可逆。与匹吲哚不同，脱氢匹吲哚不仅可作为MAO-A抑制剂，还可作为氯氮平样的选择性GABAA受体阻断剂，优先阻断对二甲基氯苯哌嗪（DMCM）或Ro 5 - 4864不敏感的一部分GABAA受体。
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