Inhibition of the NMDA and AMPA receptor channels by antidepressants and antipsychotics

被引:47
|
作者
Barygin, Oleg I. [1 ]
Nagaeva, Elina I. [1 ]
Tikhonov, Denis B. [1 ]
Belinskaya, Darya A. [1 ]
Vanchakova, Nina P. [1 ,2 ]
Shestakova, Natalia N. [1 ]
机构
[1] RAS, IM Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg, Russia
[2] Pavlov State Med Univ, St Petersburg, Russia
关键词
Ionotropic glutamate receptors; Antidepressants; Patch-clamp; Inhibition; Mechanisms; Neuropathic pain; POSTHERPETIC NEURALGIA; DOUBLE-BLIND; FLUOXETINE; PAIN; AMITRIPTYLINE; DESIPRAMINE; CITALOPRAM; MANAGEMENT; CURRENTS; BLOCKER;
D O I
10.1016/j.brainres.2017.01.028
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
It is known that some antidepressants and antipsychotics directly inhibit NMDA-type ionotropic glutamate receptors. In this study we systematically studied action of seven drugs (Fluoxetine, Citalopram, Desipramine, Amitriptyline, Atomoxetine, Chlorpromazine, and Clozapine) on NMDA receptors and Ca2+ -permeable and-impermeable AMPA receptors in rat brain neurons by whole-cell patch-clamp technique. Except for weak effect of fluoxetine, all drugs were virtually inactive against Ca2+-impermeable AMPA receptors. Fluoxetine and desipramine significantly inhibited Ca2+-permeable AMPA receptors (IC50 = 43 +/- 7 and 105 +/- 12 mu M, respectively). Desipramine, atomoxetine and chlorpromazine inhibited NMDA receptors in clinically relevant low micromolar concentrations, while citalopram had only weak effect. All tested medicines have been clustered into two groups by their action on NMDA receptors: desipramine, amitriptyline, chlorpromazine, and atomoxetine display voltage- and magnesium-dependent open channel blocking mechanism. Action of fluoxetine and clozapine was found to be voltage- and magnesium-independent. All voltage-dependent compounds could be trapped in closed NMDA receptor channels. Possible contribution of NMDA receptor inhibition by certain antidepressants and antipsychotics to their analgesic effects in neuropathic pain is discussed. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:58 / 66
页数:9
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