Elmorsy Ekramy, Smith Paul A
School of Life Science, University of Nottingham Medical School, Queens Medical Centre, Nottinghamshire, NG7 2UH, UK; Departments of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Egypt.
School of Life Science, University of Nottingham Medical School, Queens Medical Centre, Nottinghamshire, NG7 2UH, UK.
Biochem Biophys Res Commun. 2015 May 8;460(3):857-62. doi: 10.1016/j.bbrc.2015.03.122. Epub 2015 Mar 28.
Antipsychotics (APs) are widely used medications, however these are not without side effects such as disruption of blood brain barrier function (BBB). To investigate this further we have studied the chronic effects of the typical APs, chlorpromazine (CPZ) and haloperidol (HAL) and the atypical APs, risperidone (RIS) and clozapine (CLZ), on the bioenergetics of human micro-vascular endothelial cells (HBVECs) of the BBB. Alamar blue (AB) and ATP assays showed that these APs impair bioenergenesis in HBVECs in a concentration and time dependent manner. However since these effects were incomplete they suggest a population of cell bioenergetically heterogeneous, an idea supported by the bistable nature by which APs affected the mitochondrial transmembrane potential. CPZ, HAL and CLZ inhibited the activity of mitochondrial complexes I and III. Our data demonstrates that at therapeutic concentrations, APs can impair the bioenergetic status of HBVECs, an action that help explains the adverse side effects of these drugs when used clinically.
抗精神病药物（APs）是广泛使用的药物，然而这些药物并非没有副作用，如破坏血脑屏障功能（BBB）。为了进一步研究这一问题，我们研究了典型抗精神病药物氯丙嗪（CPZ）和氟哌啶醇（HAL）以及非典型抗精神病药物利培酮（RIS）和氯氮平（CLZ）对血脑屏障人微血管内皮细胞（HBVECs）生物能量学的慢性影响。alamar蓝（AB）和ATP检测表明，这些抗精神病药物以浓度和时间依赖性方式损害HBVECs中的生物能量生成。然而，由于这些影响并不完全，它们表明细胞群体在生物能量学上存在异质性，这一观点得到了抗精神病药物影响线粒体跨膜电位的双稳态性质的支持。CPZ、HAL和CLZ抑制线粒体复合物I和III的活性。我们的数据表明，在治疗浓度下，抗精神病药物会损害HBVECs的生物能量状态，这一作用有助于解释这些药物在临床使用时的不良副作用。
