Referenced in: none

Automatically associated channels: Cav1.1 , Slo1

Title: Chlorpromazine confers neuroprotection against brain ischemia by activating BKCa channel.

Authors: Hua-Juan Li, Yu-Jiao Zhang, Li Zhou, Feng Han, Ming-Yan Wang, Mao-Qiang Xue, Zhi Qi

Journal, date & volume: Eur. J. Pharmacol., 2014 Jul 15 , 735, 38-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24755143

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.