title: Thioxanthenes, chlorprothixene and flupentixol inhibit proton currents in BV2 microglial cells.
abstract: The thioxanthene antipsychotic drugs chlorprothixene and flupentixol have anti-inflammatory and antioxidant properties. The reactive oxygen species produced by NADPH oxidase during microglia-mediated inflammatory responses cause neuronal damage, thereby contributing to various neurodegenerative diseases. Voltage-gated proton channels sustain the NADPH oxidase activity, and inhibition of the channels' activity reduces the production of reactive oxygen species. Herein, the effects of chlorprothixene and flupentixol on proton currents were investigated in BV2 microglial cells using the whole-cell patch-clamp method. Both drugs inhibited the proton currents in a concentration-dependent manner (IC50=1.7μM and 6.6μM, respectively). Chlorprothixene at 3μM slightly shifted the activation voltage toward depolarization. Both the activation and the deactivation kinetics of the proton currents were slowed by chlorprothixene 1.2- and 3.5-fold, respectively. Thus, the inhibition of proton currents may be partly responsible for the antioxidant effects of thioxanthene antipsychotic drugs.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 06974, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 06974, Republic of Korea. Electronic address: jinhos@cau.ac.kr.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Song
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002749:Chlorprothixene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D005475:Flupenthixol / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D011522:Protons
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D011522:Protons; D002749:Chlorprothixene; D005475:Flupenthixol
keywords: Chlorprothixene; Flupentixol; Microglia; Proton channel; Thioxanthenes