Spinal Cord and Brain Injury Research Center, Department of Anatomy and Neurobiology, University of Kentucky, 741. S. Limestone Street, Lexington, KY 40536-0509, USA.
Neuromolecular Med. 2011 Mar;13(1):31-6. doi: 10.1007/s12017-010-8130-x. Epub 2010 Jul 13.
Dimebon was originally introduced as an antihistamine and subsequently investigated as a possible therapeutic for a variety of disorders, including Alzheimer's disease. One putative mechanism underlying the neuroprotective properties of Dimebon is inhibition of mitochondrial permeability transition, based on the observation that Dimebon inhibited the swelling of rat liver mitochondria induced by calcium and other agents that induce permeability transition. Because liver and brain mitochondria differ substantially in their properties and response to conditions associated with opening of the permeability transition pore, we sought to determine whether Dimebon inhibited permeability transition in brain mitochondria. Dimebon reduced calcium-induced mitochondrial swelling but did not enhance the calcium retention capacity or impair calcium-induced cytochrome C release from non-synaptic mitochondria isolated from rat brain cerebral cortex. These findings indicate that Dimebon does not inhibit mitochondrial permeability transition, induced by excessive calcium uptake, in brain mitochondria.
地美溴铵最初被用作抗组胺药，随后被研究作为治疗多种疾病的药物，包括阿尔茨海默病。地美溴铵具有神经保护作用的一个假定机制是抑制线粒体通透性转换，这基于地美溴铵抑制由钙和其他诱导通透性转换的试剂诱导的大鼠肝线粒体肿胀的观察结果。因为肝线粒体和脑线粒体在性质和对与通透性转换孔开放相关的条件的反应上有很大差异，所以我们试图确定地美溴铵是否抑制脑线粒体中的通透性转换。地美溴铵减少了钙诱导的线粒体肿胀，但不增强钙保留能力，也不损害从大鼠大脑皮层分离的非突触线粒体中钙诱导的细胞色素 C 释放。这些发现表明，地美溴铵不抑制脑线粒体中由过量钙摄取诱导的线粒体通透性转换。
