title: Chlorpromazine confers neuroprotection against brain ischemia by activating BKCa channel.
abstract: Chlorpromazine (CPZ) is a well-known antipsychotic drug, still widely being used to treat symptoms of schizophrenia, psychotic depression and organic psychoses. We have previously reported that CPZ activates the BKCa (KCa1.1) channel at whole cell level. In the present study, we demonstrated that CPZ increased the single channel open probability of the BKCa channels without changing its single channel amplitude. As BKCa channel is one of the molecular targets of brain ischemia, we explored a possible new use of this old drug on ischemic brain injury. In middle cerebral artery occlusion (MCAO) focal cerebral ischemia, a single intraperitoneal injection of CPZ at several dosages (5mg/kg, 10mg/kg and 20mg/kg) could exert a significant neuroprotective effect on the brain damage in a dose- and time-dependent manner. Furthermore, blockade of BKCa channels abolished the neuroprotective effect of CPZ on MCAO, suggesting that the effect of CPZ is mediated by activation of the BKCa channel. These results demonstrate that CPZ could reduce focal cerebral ischemic damage through activating BKCa channels and merits exploration as a potential therapeutic agent for treating ischemic stroke.
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China.
authors.forename: Hua-Juan
authors.initials: HJ
authors.lastname: Li
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China.
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China.
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China. Electronic address: xmq8887@xmu.edu.cn.
authors.forename: Mao-Qiang
authors.initials: MQ
authors.lastname: Xue
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China. Electronic address: qizhi@xmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002746:Chlorpromazine / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley
chemical_list: C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D018696:Neuroprotective Agents; D002746:Chlorpromazine
keywords: BK(Ca) channels (K(Ca)1.1); Brain ischemia; Chlorpromazine; Middle cerebral artery occlusion