Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10065, USA.
Neurochem Int. 2010 Jan;56(2):208-12. doi: 10.1016/j.neuint.2009.10.006. Epub 2009 Oct 21.
Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca(2+)-induced mitochondrial permeability transition in rat liver mitochondria. We investigated whether PMZ could protect against the neurotoxic effects induced by 3-nitropropionic acid (3-NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP were treated with PMZ. The findings indicate that chronic PMZ treatment significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic neurons and number of apoptotic cells in the striatum. PMZ showed a strong neuroprotective effect against 3-NP toxicity in vivo.
苯海拉明（PMZ），一种经美国食品药品监督管理局批准的抗组胺药物，在国家神经病学和中风研究所的筛选项目中被鉴定为一种具有潜在神经保护作用的化合物。研究表明，它可以预防小鼠的缺血，延迟肌萎缩侧索硬化症小鼠模型中的疾病发作，并抑制大鼠肝线粒体中的 Ca（2+）诱导的线粒体通透性转换。我们研究了 PMZ 是否可以预防 3-硝基丙酸（3-NP）诱导的神经毒性，3-NP 是一种琥珀酸脱氢酶抑制剂，用于在大鼠中模拟亨廷顿病（HD）。接受慢性皮下输注 3-NP 的刘易斯大鼠接受 PMZ 治疗。研究结果表明，慢性 PMZ 治疗显著减少了纹状体中的 3-NP 诱导的病变体积、GABA 能神经元的丢失和纹状体中的凋亡细胞数量。PMZ 对体内 3-NP 毒性具有很强的神经保护作用。
