Clozapine and olanzapine inhibit proton currents in BV2 microglial cells

European Journal of Pharmacology
Hyewon ShinJin-Ho Song

Abstract

Excessive reactive oxygen species produced by NADPH oxidase in over-activated microglia can lead to neuronal death. Some atypical antipsychotic drugs possibly have anti-inflammatory properties and suppress the production of pro-inflammatory cytokines and reactive oxygen species from microglia. Voltage-gated proton channels (Hv1) are expressed in microglia and are required for NADPH oxidase-dependent reactive oxygen species generation, which could contribute to neuronal death and ischemic brain damage. In the present study, we examined the effects of the atypical antipsychotics clozapine, olanzapine and risperidone on proton currents in microglial BV2 cells. Clozapine and olanzapine inhibited proton currents with IC50 values of 9.8 μM and 84 μM, respectively. Risperidone, however, showed very weak inhibition of proton currents. Clozapine-induced inhibition of proton currents was not accompanied by a positive shift in the activation voltage or reversal potential, indicating that the inhibition was not mediated through an increase in the intracellular pH. Clozapine binds to a multitude of receptors, including serotonin, dopamine and muscarinic receptors. Serotonin receptors, however, were not responsible for the proton current inh...Continue Reading

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Citations

Mar 8, 2016·European Journal of Pharmacology·Jiwon Kim, Jin-Ho Song
Jun 5, 2016·Molecular Pharmacology·Audry FernándezCarlos Gonzalez
Oct 30, 2016·Neuroscience Letters·Yuzuki KandaMasayuki Ikeda
Nov 12, 2017·European Archives of Psychiatry and Clinical Neuroscience·G FondUNKNOWN FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group
Sep 7, 2018·Frontiers in Cellular Neuroscience·Md Ezazul HaqueDong-Kug Choi
Dec 17, 2020·Pharmaceuticals·Giuseppe CarusoFilippo Caraci
Apr 27, 2021·Frontiers in Cellular Neuroscience·Junyun HeJunfang Wu

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