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81.
Isoherranen N Spiegelstein O Bialer M Zhang J Merriweather M Yagen B Roeder M Triplett AA Schurig V Finnell RH 《Epilepsia》2003,44(10):1280-1288
PURPOSE: The purpose of this study was to test the teratogenic potential of the antiepileptic drug (AED) levetiracetam (LEV), its major metabolite in humans, 2-pyrrolidone-N-butyric acid (PBA), and enantiomer, (R)-alpha-ethyl-oxo-pyrrolidine acetamide (REV), in a well-established mouse model. METHODS: All compounds were administered by intraperitoneal injections once daily to SWV/Fnn mice on gestational days 8-1/2 to 12-1/2. LEV was administered at doses of 600, 1,200, and 2,000 mg/kg/day, piracetam (PIR) and PBA, at 600 and 1,200 mg/kg/day, and REV, at 600 mg/kg/day. On gestational day 18(1/2), fetuses were examined for gross external malformations and prepared for skeletal analysis by using Alizarin Red S staining. RESULTS: No significant gross external malformations were observed in any of the study groups. Fetal weights were significantly reduced in most study groups. Resorption rates were significantly increased only in the 2,000-mg/kg/day LEV group. The overall incidence of skeletal abnormalities and specifically of hypoplastic phalanges was significantly increased in both PBA treatments and in the intermediate 1,200-mg/kg/day LEV group. In contrast to that in humans, 24-h urinary excretion analysis in mice showed that 65-100% of the LEV doses were excreted unchanged, whereas only 4% was excreted as the metabolite PBA. CONCLUSIONS: Results of this study demonstrate that both LEV and its major metabolite in humans, PBA, do not induce major structural malformations in developing SWV/Fnn embryos and suggest that they provide a margin of reproductive safety for the pregnant epileptic population when compared with other AEDs tested in this mouse model. 相似文献
82.
金思维治疗社区轻度认知损害老年患者记忆减退症状的1年随访 总被引:15,自引:1,他引:15
目的 :观察中药复方制剂金思维对轻度认知损害老年患者记忆减退的治疗效果。方法 :应用临床痴呆评定表在老年及老年前期人群中筛选出轻度认知损害 (CDR =0.0/0.5分 )患者 75例 ,随机分为中药观察组 (n=30例 )、阳性对照组 (n=30例 )、安慰剂组 (n =15例 )。采用单盲双模拟对照法 ,观察组口服金思维丸 ,4粒 /次 ,3次 /d ,安慰剂 2片 /次 ,3次 /d。阳性对照组口服脑复康片 ,2片 /次 ,3次 /d ,安慰剂 4丸 /次 ,3次 /d。安慰剂组口服安慰剂 4丸 +2片 /次 ,3次 /d。分别在基线点和终末点 (服药 3个月后 )以及随访点 (停药 1年后 )进行神经心理学评价。用MMSE和Bristol最新神经心理学成套量表的记忆部分项目评价记忆状态。结果 :金思维组 3个月后MMSE分值从 27.50±1.68提高到 28.27±1.70 ,1年后降至 26.90±1.90 ,但与安慰剂组 26.33±1.03比较仍有显著性差异 (P<0.05) ,与脑复康组比较无显著性意义。 1年后 ,金思维组词语记忆积分从 68.73±28.74显著性提高到 87.33± 29.78,与安慰剂组比较有非常显著性差异 (P<0.01) ;记忆总分也从 78.2 3±28.98提高到 93.53±35.56 ,明显高于脑复康组 (P<0.05)和安慰剂组 (P<0 .01)。结论 :金思维具有改善和延缓轻度认知损害。 相似文献
83.
To clarify the question whether the duration of hypoxia exposure has an influence on the point in time or the strength of hypoxic preconditioning, hypoxia exposure of rats lasting 1 and 8 h was tested regarding the modification of susceptibility to acute pentylenetetrazol-induced seizures. Following the short-lasting (1 h) hypoxia, the maximum level of preconditioning action was observed 7 days after hypoxia, whereas the longer-lasting hypoxia (8 h) produced the maximum level of protection 14 days after hypoxia. We investigated the influence of fucose and piracetam on the effect of hypoxia preconditioning by the application of the substances 20 min before the beginning of hypoxia exposure. Fucose did not modify the result of hypoxia preconditioning. But after the treatment with piracetam, the preconditioning effect was prevented following hypoxia lasting 1 and 8 h. We suggest that the radical scavenger properties of piracetam are responsible for the absence of protection against pentylenetetrazol-evoked seizures. 相似文献
84.
Otto L. Wolthuis 《Pharmacology, biochemistry, and behavior》1981,15(2):247-255
The effects of etiracetam, a structural analogue of piracetam, were investigated in rats on Y-maze discrimination acquisition, on open field behaviour, on one-trial passive avoidance learning and on shuttlebox acquisition and extinction. The results indicate that this drug significantly enhances acquisition and may improve retention without having any detectable effects on spontaneous behaviour, not even in very high doses (500 mg/kg IP). Sensitivity to footshock, measured as “flinch” thresholds, was not altered by etiracetam in doses of 25 or 100 mg/kg IP. For a shuttlebox task the effective dose-range lies between 20–30 mg/kg IP, provided pretreatment during 4 days is given. Without pretreatment, i.e. when the drug is only administered during the relatively fast acquisition in the shuttlebox, it was found that acquisition was not enhanced, but extinction of the acquired behaviour was significantly inhibited. The effects of etiracetam can be found at lower dose-levels than with piracetam and also in tests (passive avoidance, shuttlebox) in which piracetam has no or only marginal effects. 相似文献
85.
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87.
目的:比较奥拉西坦和吡拉西坦治疗老年脑出血后认知功能障碍的临床疗效和安全性。方法上海中冶职工医院2012年2月-2013年12月收治的老年脑出血患者104例,随机分为对照组和治疗组,每组各52例。对照组口服吡拉西坦片,4片/次,3次/d。治疗组口服奥拉西坦胶囊,2粒/次,3次/d。两组均持续治疗6个月。分别于治疗前后采用蒙特利尔认知评估(MoCA)量表、简易智能精神状态检查(MMSE)量表和日常生活活动(ADL)量表进行认知功能评定。结果治疗后,两组 MoCA、MMSE 量表的项目评分均较治疗前显著提高,同组治疗前后差异有统计学意义(P<0.05);治疗后,治疗组MoCA量表中执行功能、计算评分高于对照组;治疗组MMSE量表中即刻回忆力、注意计算力、语言能力、总分均高于对照组,两组比较差异有统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义。结论奥拉西坦较吡拉西坦可更好的改善老年脑出血后患者的认知功能障碍,且不良反应较少,具有良好的临床疗效和安全性。 相似文献
88.
局灶性脑缺血时吡拉西坦对缺血半球能量代谢的影响 总被引:4,自引:1,他引:4
目的 观察吡拉西坦对局灶性脑缺血时缺血半球能量代谢的影响。方法 采用动脉腔内插线大鼠局灶性脑缺血模型及测定缺血 2 h/再灌注 2 h后缺血半球内乳酸 ( L A)水平、乳酸脱氢酶 ( L DH)和肌酸激酶 ( CK)活性的变化 ,HE染色结合图像分析测定缺血后 2 4h的梗死体积。结果 吡拉西坦 ( 2 0 0 mg/kg)可明显降低缺血半球内 L A水平 ,增加 L DH的活性 ,对 CK活性无明显影响 ,它可明显降低缺血 2 h/再灌注 2 2 h后的皮质、皮质下结构和半球的梗死体积。结论 吡拉西坦具有明确的抗局灶性脑缺血作用 ,它可明显改善缺血组织的能量代谢状态 ,增加 L DH的活性 ,减轻乳酸堆积及组织酸中毒 ,缩小梗死体积。 相似文献
89.
90.
目的 观察吡拉西坦联合盐酸多奈哌齐治疗血管性认知障碍(VCI)患者的临床疗效.方法 选取2018-03—2020-02安阳市人民医院收治VCI患者114例为研究对象,按随机数表法分为联合组及对照组各57例.对照组患者给予单纯吡拉西坦治疗,联合组患者给予吡拉西坦联合盐酸多奈哌齐治疗,观察治疗前后2组认知功能、日常生活能力... 相似文献