Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY 40202, United States.
Psychiatry Res. 2011 Aug 15;188(3):366-71. doi: 10.1016/j.psychres.2010.12.030. Epub 2011 Jan 26.
Memantine, a selective antagonist of the N-methyl-D-aspartate receptor, is approved for the treatment of moderate to severe Alzheimer's disease. Ion dysregulation is thought to be involved in the pathophysiology of bipolar illness, suggesting that memantine may be effective in treating bipolar manic and/or depressive episodes. We utilized two preclinical models of mania that mimic pathophysiologic changes seen in bipolar illness to examine the potential efficacy of memantine in the treatment of this disorder. Locomotor hyperactivity of male Sprague-Dawley rats in an open field was induced with intracerebroventricular (ICV) administration of 10(-3) M ouabain. Memantine (2.5, 5 or 7.5mg/kg), lithium (6.75 mEq/kg), or vehicle were administered acutely via intraperitoneal injection immediately prior to ouabain, then chronically for 7 days (oral memantine 20, 30, and 40 mg/kg/day in water; lithium 2.4 g/kg food). In a second model of bipolar disorder, cycling between population spikes and epileptiform bursts was investigated in rat hippocampal slices treated with ouabain (3.3 μM) alone or in combination with memantine (0.5, 1.0, and 5.0 μM). Ouabain-induced hyperlocomotion was normalized with acute and chronic lithium and chronic use of memantine. Memantine delayed the onset of ouabain-induced-cycling in hippocampal slices. Memantine may have antimanic properties.
美金刚是一种 N-甲基-D-天冬氨酸受体选择性拮抗剂，被批准用于治疗中重度阿尔茨海默病。离子失调被认为与双相情感障碍的病理生理学有关，这表明美金刚可能对治疗双相情感障碍的躁狂和/或抑郁发作有效。我们利用两种模拟双相情感障碍中所见病理生理变化的躁狂前临床模型，来研究美金刚治疗这种疾病的潜在疗效。雄性 Sprague-Dawley 大鼠在开放场中的运动活性增加是通过侧脑室（ICV）给予 10（-3）M 哇巴因诱导的。美金刚（2.5、5 或 7.5mg/kg）、锂（6.75mEq/kg）或载体在哇巴因给药前立即通过腹腔内注射急性给药，然后连续 7 天（口服美金刚 20、30 和 40mg/kg/天在水中；锂 2.4g/kg 食物）。在双相情感障碍的第二个模型中，在单独用哇巴因（3.3μM）或与美金刚（0.5、1.0 和 5.0μM）联合处理的大鼠海马切片中研究了种群峰和癫痫样爆发之间的循环。急性和慢性锂以及慢性使用美金刚可使哇巴因诱导的过度运动正常化。美金刚延迟了海马切片中哇巴因诱导循环的发作。美金刚可能具有抗躁狂作用。
