Department of Pharmacology and Toxicology, Alzheimer's Research Center, Medical College of Georgia, Augusta, USA.
Br J Pharmacol. 2011 Oct;164(3):970-8. doi: 10.1111/j.1476-5381.2011.01432.x.
Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we examined the acute effect of dimebolin on components of working memory in non-human primates, young adult (11-17 years old) and aged (20-31 years old) rhesus macaques.
The effects of dimebolin (3.9-118 µg kg(-1)) on working memory, as measured by performance on delayed matching-to-sample (DMTS), were examined in the normal young adult monkeys and aged adult monkeys. All the monkeys studied were proficient in the performance of a computer-assisted DMTS task. In a subsequent experiment in the same subjects, dimebolin was administered 15 min before a cognitively-impairing dose (20 µg kg(-1)) of scopolamine.
In both the young adult and aged monkeys, dimebolin significantly increased the DMTS task accuracies. In young adults, the task improvement was associated with long (retention/retrieval) delay trials, and a protracted enhancement was observed for sessions run 24 h post administration of a single dose. Dimebolin did not significantly attenuate the scopolamine-induced impairment. In the aged monkeys, dimebolin significantly improved the reduced task accuracies associated with long delay intervals.
Here we demonstrated that dimebolin is able to improve components of working memory in monkeys and to induce a protracted response for at least 24 h after administration of a single dose.
地美波隆（拉替拉嗪）是一种具有多种潜在药物靶点的化合物，正在临床试验中评估其治疗阿尔茨海默病（AD）的疗效，初步结果表明它可以减缓疾病进程。还有证据表明地美波隆可以直接改善认知的某些方面。在这里，我们研究了地美波隆对年轻成年（11-17 岁）和老年（20-31 岁）恒河猴工作记忆成分的急性影响。
通过延迟匹配样本（DMTS）任务来衡量工作记忆，检测了地美波隆（3.9-118 µg kg(-1))对正常年轻成年猴和老年成年猴工作记忆的影响。所有接受研究的猴子都擅长计算机辅助 DMTS 任务。在同一组猴子的后续实验中，地美波隆在认知障碍剂量（20 µg kg(-1))的东莨菪碱给药前 15 分钟给药。
在年轻成年和老年猴子中，地美波隆均显著提高了 DMTS 任务的准确性。在年轻成年人中，任务改善与长（保留/检索）延迟试验有关，并且在单次给药后 24 小时进行的会话中观察到了延长的增强。地美波隆没有显著减弱东莨菪碱引起的损伤。在老年猴子中，地美波隆显著改善了与长延迟间隔相关的降低的任务准确性。
在这里，我们证明了地美波隆能够改善猴子的工作记忆成分，并在单次给药后至少 24 小时内引起持续的反应。
