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91.
Yunomae K Ichisaki S Matsuo J Nagayama S Fukuzaki K Nagata R Kito G 《Journal of applied toxicology : JAT》2007,27(1):78-85
It is presumed that phosphodiesterase (PDE) inhibitors have two mechanisms for inhibition of hERG currents in the acute applications to cells: direct channel block, and downregulation of human ether-a-go-go related gene (hERG) activities by PKA-dependent pathway mediated phosphorylation through their inhibitory effects against PDE enzymes. However, it is unknown whether PDE inhibition contributes to the inhibitory effects of PDE inhibitors on hERG currents. This study examined the effects of various PDE inhibitors on hERG currents using both the whole-cell and perforated patch-clamp techniques in hERG transfected CHO-K1 cells. The study also investigated the contribution of the PKA-dependent pathway to the inhibitory effects of PDE inhibitors on hERG currents. Of the PDE inhibitors tested, vinpocetine, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), vesnarinone, rolipram and dipyridamole decreased hERG currents in a concentration-dependent manner. Vinpocetine and vesnarinone markedly decreased the hERG current with an IC (50)of 0.13 and 20.6 microm, respectively, at comparatively low concentrations. Furthermore, vinpocetine caused a cumulative block of hERG currents. Milrinone, amrinone and zaprinast had no effect on the hERG current up to 100 microm. Of the PDE3 inhibitors (vesnarinone, amrinone and milrinone), only vesnarinone showed an hERG inhibitory effect. The inhibitory effects of vinpocetine and vesnarinone were not significantly affected by the co-application of protein kinase inhibitors. Furthermore, the protein kinase activators had no effect on hERG currents. It is concluded that vinpocetine and vesnarinone block the hERG channel directly, and that the inhibitory effect on intracellular PDE in the PKA-dependent pathway may not be involved in the inhibition of hERG currents in hERG transfected CHO-K1 cells. 相似文献
92.
长春西汀(Vinpocetine)具有高脂溶性,易通过血脑屏障进入脑组织,能改善、恢复缺血性脑血管病患者血流速度,提高卒中患者脑灌注及脑组织摄氧能力,改善脑代谢。由于该药具有优良的临床药理疗效,临床应用范围日益广泛。本文对该药的临床应用的最新进展情况加以综述。 相似文献
93.
94.
Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial 总被引:3,自引:0,他引:3
V. L. Feigin B. M. Doronin T. F. Popova E. V. Gribatcheva D. V. Tchervov 《European journal of neurology》2001,8(1):81-85
The aim of the study was to assess the safety and feasibility of a clinical trial on the effect of vinpocetine, a synthetic ethyl ester of apovincamine, in acute ischaemic stroke. Thirty consecutive patients with computed tomography verified diagnosis of acute ischaemic stroke, who could receive drug treatment within 72 h of stroke onset, were enrolled. The patients were randomly allocated to receive either low-molecular weight dextran alone or in combination with vinpocetine. Poor outcome was defined as being dead or having a Barthel index of < 70 or a Rankin score of 3--5. Intention-to-treat analysis was applied. One-tenth of all hospitalized patients with acute ischaemic stroke were eligible for the trial. Thirty eligible patients were treated with either low-molecular weight dextran alone (mean age 57.9 +/- 11.6 years, n = 15) or in combination with vinpocetine (mean age 60.8 +/- 6.6 years, n = 15). The two treatment groups were comparable with respect to major prognostic variables. A relative risk (RR) reduction of poor outcome at 3 months follow-up was 30% (RR = 0.7; 95% confidence interval [CI] 0.1--3.4), as defined by the modified Barthel Index, and 60% as defined by the modified Ranking score (RR = 0.4, 95% CI: 0.1--1.7). The National Institute of Health (NIH--NINDS) Stroke Scale score was marginally significantly better in the vinpocetine treated group at 3 months of follow-up (P = 0.05, ANOVA). No significant adverse effects were seen. This pilot study shows that a full-scale randomized double-blind, placebo-controlled trial of vinpocetine treatment in acute ischaemic stroke is feasible and warranted. 相似文献
95.
96.
目的 建立和验证UPLC-MS/MS测定人血浆中长春西汀和阿朴长春胺酸的方法,并用于临床样品检测。方法 以长春西汀-d5、阿朴长春胺酸-d4为内标,人血浆样品经蛋白沉淀法沉淀处理,色谱柱为Waters ACQUITY UPLC?BEH C18(2.1 mm×50 mm,1.7μm),流动相为乙腈-水(含0.05%甲酸),梯度洗脱,流速0.35 mL·min-1;电喷雾离子化源正离子监测模式。结果 长春西汀和阿朴长春胺酸线性范围分别为0.04~20.0 ng·mL-1(r=0.999 7)、0.50~250 ng·mL-1(r=0.999 6),检测限分别为0.01,0.10 ng·mL-1,待测物与内标提取回收率均为94.81%~105.0%,基质效应为94.51%~105.0%,RSD均<5%;批内、批间精密度RSD均<10%。结论 本法特异性强、快速、准确,重复性好,适用于长春西汀临床生物样品检测及生物等效性研究。 相似文献