比较的影响tak - 147 (zanapezil)和e - 2020(多奈哌齐)细胞外腹侧海马乙酰胆碱水平和血液流动的自由移动的老鼠。

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Hatip-Al-Khatib我,隆,Egashira N, Iwasaki K,藤原M

比较的影响tak - 147 (zanapezil)和e - 2020(多奈哌齐)细胞外腹侧海马乙酰胆碱水平和血液流动的自由移动的老鼠。

大脑研究》2004年6月25日,1012 (2):169 - 76。

PubMed ID

15158174 (在PubMed

]

文摘

zanapezil的影响(tak - 147)和多奈哌齐(E2020)细胞外乙酰胆碱(ACh)水平调查HPLC-microdialysis腹侧海马(VH)的自由移动的完整的老鼠。结果表明,基底ACh VH释放率是116.7 + / - 12.4到158.4 + / - 22.86 fmol / 20 microl。2、5和10毫克/公斤,单一的订单。,每个药物乙酰胆碱水平增加了9.4%,106.5%,50.8% (tak - 147)和14.8%、76.1%,分别为120.94% (E2020)。ED50值是4.52毫克/公斤(1.43 - 14.29;R = 0.52)和4.07毫克/公斤(1.77 - 9.37;为tak - 147和E2020 R = 0.985),分别。分析数据显示,相对tak - 147 / E2020效力比率是0.773,但E2020伴随着更加突出的影响骨骼肌自发性收缩,咬,增加排便以及较小程度上的唾液分泌。此外,显著影响tak - 147(20分钟)比早些时候观察E2020(60分钟)。在这项研究中,我们还研究了这两种药物的效果5毫克/公斤以上的剂量使用激光多普勒Flowmetry VH血液流动。 The results showed that the average blood flow rate in the VH is 6.5 +/- 0.9 ml/min/100 g. TAK-147 did not change blood flow, but E2020 increased blood flow in a biphasic manner. The first increment was obtained between 5 and 40 min (11.5 +/- 2.2 to 12.7 +/- 2.2 ml/min/100 g), and the second one 80-105 min (10.7 +/- 1.6 to 13.4 +/- 3.6 ml/min/100 g). In conclusion, the present results indicate that both TAK-147 and E2020 increase ACh level in the VH. E2020 showed greater potency than TAK-147, but it induced more fasciculation and other side effects than TAK-147. Moreover, the blood flow increasing properties of E2020 could be beneficial in some patients with Alzheimer' disease especially those with chronic vascular dementia, but at the same time, it could also indicate less specific ACh increasing activity than TAK-147 and higher risk of cerebral hemorrhage. On the other hand, the fast and specific effect of TAK-147 may be useful for cure of early stages of Alzheimer's disease (AD).

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药物

Zanapezil