Stein Christoph, Hopfeld Julia, Lau Helene, Klein Jochen
Department of Pharmacology, College of Pharmacy, Goethe University Frankfurt, Germany.
J Pharm Pharm Sci. 2015;18(4):634-46. doi: 10.18433/j3wc8v.
Ginkgo extract EGb 761 and cholinesterase inhibitors have been shown to be effective in the treatment of dementia patients. In addition to neuroprotective effects, Ginkgo extract EGb 761 has been reported to elevate brain levels of certain neurotransmitters such as dopamine, noradrenaline, and acetylcholine. In the present study, we investigated the impact of EGb 761, donepezil and the combination of both drugs on the central cholinergic system in aged rats.
24 month old rats received EGb 761 (100 mg/kg/day), donepezil (1.5 mg/kg/day), the combination of both drugs or vehicle control by oral gavage for 14 days. We used microdialysis in rat hippocampus to monitor extracellular concentrations of acetylcholine (ACh), choline, glucose and lactate. Brain homogenates were prepared to measure activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and high affinity choline uptake (HACU).
While EGb 761 alone had no effect, donepezil and the combination of donepezil and EGb 761 increased basal ACh levels by 2- to 3-fold. Concomitantly, significant reductions of AChE and HACU were measured in both groups. No differences were seen between donepezil and the combination in these parameters. Treatment with EGb 761 decreased extracellular choline release and showed a tendency to moderately elevate ChAT activity.
We found that donepezil and EGb 761 do not display a pharmacological interaction when given together. Adding EGb 761 did not modify the effects of donepezil on the hippocampal cholinergic system. Reduced choline levels indicate neuroprotective properties of EGb 761. Therefore, the combination of EGb 761 and donepezil may be beneficial in the treatment of Alzheimer's disease (AD). This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
银杏提取物EGb 761和胆碱酯酶抑制剂已被证明对痴呆患者有效。除了神经保护作用外，据报道银杏提取物EGb 761还能提高大脑中某些神经递质的水平，如多巴胺、去甲肾上腺素和乙酰胆碱。在本研究中，我们调查了EGb 761、多奈哌齐以及两种药物联合使用对老年大鼠中枢胆碱能系统的影响。
24月龄大鼠通过灌胃接受EGb 761（100毫克/千克/天）、多奈哌齐（1.5毫克/千克/天）、两种药物的联合制剂或溶剂对照，持续14天。我们使用大鼠海马体微透析技术监测乙酰胆碱（ACh）、胆碱、葡萄糖和乳酸的细胞外浓度。制备脑匀浆以测量乙酰胆碱酯酶（AChE）、胆碱乙酰转移酶（ChAT）的活性以及高亲和力胆碱摄取（HACU）。
单独使用EGb 761没有效果，而多奈哌齐以及多奈哌齐与EGb 761的联合制剂使基础ACh水平提高了2至3倍。同时，两组中AChE和HACU均显著降低。在这些参数上，多奈哌齐与联合制剂之间没有差异。用EGb 761治疗可减少细胞外胆碱释放，并显示出适度提高ChAT活性的趋势。
我们发现多奈哌齐和EGb 761联合使用时不表现出药理相互作用。添加EGb 761不会改变多奈哌齐对海马胆碱能系统的作用。胆碱水平降低表明EGb 76具有神经保护特性。因此，EGb 761和多奈哌齐联合使用可能对阿尔茨海默病（AD）的治疗有益。本文接受发表后审查。注册读者（见“读者须知”）可通过点击本期目录页面上的摘要进行评论。
