Itil T M, Eralp E, Ahmed I, Kunitz A, Itil K Z
New York Institute for Medical Research, Tarrytown 10591, USA.
Psychopharmacol Bull. 1998;34(3):391-7.
In 1994, a standardized dry extract of Ginkgo biloba leaves (SeGb), has been approved by German health authorities for the treatment of primary degenerative dementia and vascular dementia. More than 24 different brands of Ginkgo biloba extract are sold in the United States. Tacrine, also known as tetrahydroaminoacrine (THA), and donepezil are currently the only drugs approved in the United States for the treatment of Alzheimer's disease. Previous studies demonstrated that SeGb and tacrine induce significant pharmacological effects on the brains of young, healthy human males, as determined by bioelectrical activity measurements obtained using the quantitative pharmaco-electroencephalogram (QPEEG) method. The type of central nervous system (CNS) effects we have seen on computer-analyzed EEGs (CEEGs) after administration of tacrine or EGb suggests both are "cognitive activators" which are, as a class of products, characterized by a (prepost) relative increase of 7.5 to 13 Hz ("alpha") and decrease of 1.3 to 7.5 Hz ("delta" and "theta") activity. To determine whether EGb or tacrine had noticeable pharmacological effects on elderly subjects diagnosed with possible or probable Alzheimer's, the present open, uncontrolled trial was conducted. Data from 18 subjects (11 males, 7 females) at an average age of 67.4 years with light to moderate dementia (Mini Mental mean score = 23.7, ranges: 15-29 [Geriatric Depression Scale mean scores = 3.7; range: 3.2-5.4]) were analyzed for this presentation. Each subject was randomly administered a single oral "Test-Dose" of either 40 mg of tacrine or 240 mg of EGb2 in two separate sessions within 3- to 7-day intervals. Before drug administration and at 1- and 3-hour intervals after drug administration, CEEGs were recorded for a minimum of 10 minutes. The CEEGs were analyzed using Period Analysis programs we developed for QPEEG. The results indicated that both EGb and, to a lesser degree, tacrine induced pharmacological effects, as established by QPEEG measurements, in the CNS similar to those previously established in healthy, young subjects. The type of CNS effects produced by EGb (as established by HZI's CEEG psychotropic drug database) in elderly dementia patients were similar to those induced by tacrine responders as well as those seen after the administration of other "cognitive activators" (pramiracetam, vinpocetine, BMY-21502, suloctidil, and lisuride) and anti-dementia drugs approved in the United States or Europe (tacrine, donepezil, nimodipine, piracetam, and oxiracetam) from our database. The results also showed that 240 mg of EGb has typical cognitive activator CEEG profiles (responders) in more subjects (8 of 18) than 40 mg tacrine (3 of 18 subjects). Because of the small sample size, we could not test the hypothesis that subjects who showed cognitive activator-type pharmacological response to the first Test-Dose of EGb or tacrine also exhibit more therapeutic effects (compared to nonresponders) when drugs are administered chronically.
1994年，一种标准化的银杏叶干提取物（SeGb）已获德国卫生当局批准，用于治疗原发性退行性痴呆和血管性痴呆。在美国，有超过24种不同品牌的银杏叶提取物出售。他克林，也被称为四氢氨基吖啶（THA），以及多奈哌齐，是目前美国批准用于治疗阿尔茨海默病的仅有的药物。先前的研究表明，通过使用定量药物脑电图（QPEEG）方法获得的生物电活动测量结果确定，SeGb和他克林对年轻、健康的男性大脑具有显著的药理作用。我们在给予他克林或银杏叶提取物（EGb）后在计算机分析脑电图（CEEG）上看到的中枢神经系统（CNS）效应类型表明，两者都是“认知激活剂”，作为一类产品，其特征是（前后）7.5至13赫兹（“阿尔法”）的相对增加以及1.3至7.5赫兹（“德尔塔”和“西塔”）活动的减少。为了确定EGb或他克林对被诊断为可能患有或很可能患有阿尔茨海默病的老年人是否有显著的药理作用，进行了本次开放性、非对照试验。对18名受试者（11名男性，7名女性）的数据进行了分析，这些受试者平均年龄为67.4岁，患有轻度至中度痴呆（简易精神状态平均得分 = 23.7，范围：15 - 29 [老年抑郁量表平均得分 = 3.7；范围：3.2 - 5.4]），用于本次报告。每个受试者在3至7天的间隔内分两个单独的时段随机口服一次“试验剂量”，即40毫克他克林或240毫克EGb2。在给药前以及给药后1小时和3小时，记录CEEG至少10分钟。使用我们为QPEEG开发的周期分析程序对CEEG进行分析。结果表明，通过QPEEG测量确定，EGb以及程度较轻的他克林在中枢神经系统中诱导了药理作用，类似于先前在健康的年轻受试者中确定的作用。EGb（由HZI的CEEG精神药物数据库确定）在老年痴呆患者中产生的中枢神经系统效应类型与他克林反应者诱导的效应以及在给予其他“认知激活剂”（吡拉西坦、长春西汀、BMY - 21502、舒洛地尔和利苏瑞ide）以及美国或欧洲批准的抗痴呆药物（他克林、多奈哌齐、尼莫地平、吡拉西坦和奥拉西坦）后从我们的数据库中看到的效应相似。结果还表明，240毫克EGb在更多受试者（18名中的8名）中具有典型的认知激活剂CEEG特征（反应者），而40毫克他克林（18名受试者中的3名）。由于样本量小，我们无法检验这样的假设，即对EGb或他克林的首次试验剂量表现出认知激活剂类型药理反应的受试者在长期给药时（与无反应者相比）也表现出更多的治疗效果。
