Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice

Chronic treatment (2 weeks) with piracetam (500 mg/kg, once daily PO) elevatedm-cholinoceptor density in the frontal cortex of aged (18 months) female mice by about 30–40%, but had no effect onm-cholinoceptor density in the frontal cortex of young (4 weeks) mice. The effect of piracetam onm-cholinoceptor density as determined by the specific binding of tritiated QNB was not affected by concomitant daily treatment with either choline (200 mg/kg) or scopolamine (4 mg/kg). It is concluded that the effect of piracetam onm-cholinoceptor density could explain the positive effects which have been reported for combinations of cholinergic precursor treatment with piracetam on memory and other cognitive functions in aged experimental animals and patients and could also represent part of the possible mechanism of action of piracetam alone.     

Effect of piracetam on EEG spectra of boys with learning disorders

Piracetam was compared with placebo in a double-blind cross-over study of 30 learning-disabled boys. Power spectral analyses revealed that piracetam caused a decrease in the amount of delta activity and an increase in the average EEG frequency. This result is in agreement with those obtained by other workers in adult patients. Some clinical effects of piracetam may be mediated by increased alertness and/or decreased fatigue.Presented in part at the International Symposium on Nootropic Drugs in Rio de Janeiro, October 1979     

Some effects of piracetam (UCB 6215 nootropyl) on chronic schizophrenia

A study is described of effects of a nootropic drug on chronic schizophrenia. The nootropic drugs act on the central nervous system with the cerebral cortex as their target. Chronic schizophrenic patients on the drug showed improvement in object naming and in tests where the patient was required to indicate the number of times he had been tapped. Improvements were also noted in learning and memory tasks. In dichotic listening the patients showed a reduction in the amount of incorrect verbal responses produced. There were no improvements in symptom rating or social behaviour rating. These results suggest some cognitive improvement but little if any change in the disease state of the patient.     

A Pilot Study of Piracetam in Cuprophan Hemodialysis

Twelve patients, 8 male and 4 female, aged from 26 to 70 years were studied. They were on hemodialysis (HD) 4 h three times weekly with cuprophan hollow fiber dialyzers (Gambro 120M) and dialysate containing 35 mEq/L of acetate. The study compares two random HD sessions on each patient. Sixty minutes prior to one random session a placebo was administered orally, and prior to another random session piracetam was given at a dose of 8 g. Heparin dosage was not reduced during HD using QB 200 ml, QD 500 ml, and no ultrafiltration. Blood samples for leukocyte and platelet counts, serum C3, arterial paO2 and paCO2, thromboxane-B2 (TxB2), and beta-thromboglobulin (beta-TG) were taken from the arterial line before and at 15, 60, and 240 min during HD. Leukopenia at 15 min of HD was found to be less severe (p less than 0.01) in the piracetam study than in the placebo, whereas platelet count did not change. Serum C3 was slightly increased in both studies. Arterial oxygen was preserved close to the initial levels by piracetam (91.66 mm Hg versus 81.08, p less than 0.01 at 60 min, and 93.08 versus 80.17 mm Hg, p less than 0.01 at 240 min of HD sessions) but paCO2 did not change significantly. TxB2 increased less with piracetam in comparison to placebo (p less than 0.01 or p less than 0.001), but beta-TG was reduced significantly by piracetam at any time during HD (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

吡拉西坦对精神分裂症认知功能障碍的影响

目的 探讨吡拉西坦对精神分裂症患者认知功能障碍的影响.方法 将服用第一代抗精神病药物有认知功能障碍的精神分裂症患者80例随机分为研究组与对照组,各40例,研究组联合吡拉西坦治疗,对照组单独使用抗精神病药物治疗.分别于治疗前、治疗后12周进行阳性与阴性症状量表(PANSS)、数字广度测验(DST)、语词流畅性测验(VFT)、钉板实验(GPT)、连线试验A(TMT-A)及威斯康星卡片分类测验(WCST)评估.结果 研究组治疗后PANSS总分为(49.8±8.2)分,对照组为(49.4±13.3)分,均低于治疗前(P＜0.05).研究组治疗后DST为(9.22±1.94)个,VFT为(7.89±4.21)个,正确应答数为(39.49±9.83)张,均比治疗前提高(P＜0.05或P＜0.01),并且高于治疗后的对照组(P＜ 0.05或P＜0.01);持续性错误数为(20.94±7.73)张,较治疗前下降(P＜o.05),且低于同期对照组(P＜ 0.05).GPT、TMT-A以及WCST的总应答数、完成分类数治疗前后比较以及两组间同期比较差异均无统计学意义(P＞0.05).结论 吡拉西坦可部分改善精神分裂症患者的认知功能.     

Effect of Morin on pharmacokinetics of Piracetam in rats,in vitro enzyme kinetics and metabolic stability assay using rapid UPLC method

The aim of this study was to investigate the effect of Morin on the pharmacokinetics of Piracetam in rats, in vitro enzyme kinetics and metabolic stability (high throughput) studies using human liver microsomes in UPLC. For pharmacokinetics studies, male Wistar rats were pretreated with Morin (10 mg/kg) for one week and on the last day, a single dose of Piracetam (50 mg/kg) was given orally. In another group, both Morin and Piracetam were co‐administered to evaluate the acute effect of Morin on Piracetam. The control group received oral distilled water for one week and administered with Piracetam on the last day. As Morin is an inhibitor of P‐ Glycoprotein (P‐gp) and CYP 3A, it was anticipated to improve the bioavailability of Piracetam. Amazingly, relative to control, the areas under the concentration time curve and peak plasma concentration of Piracetam were 1.50‐ and 1.45‐fold, respectively, greater in the Morin‐pretreated group. However, co‐administration of Morin had no significant effect on these parameters. Apart from the aforementioned merits, the results of this study are further confirmed by clinical trials; Piracetam dosages should be adjusted to avoid potential drug interaction when Piracetam is used clinically in combination with Morin and Morin‐containing dietary supplements. The in vitro enzyme kinetics were performed to determined km, V_max & CL_ins. The in vitro metabolic stability executed for the estimation of metabolic rate constant and half‐life of Piracetam. These studies also extrapolate to in vivo intrinsic hepatic clearance (Cl_{int, in vivo}) from in vitro intrinsic hepatic clearance (CL_{int, in vitro})_. Copyright © 2012 John Wiley & Sons, Ltd.     

Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats

In an attempt to gain some insight into possible approaches to reducing age-related memory disturbances, aged Fischer 344 rats were administered either vehicle, choline, piracetam or a combination of choline or piracetam. Animals in each group were tested behaviorally for retention of a one trial passive avoidance task, and biochemically to determine changes in choline and acetylcholine levels in hippocampus, cortex and striatum. Previous research has shown that rats of this strain suffer severe age-related deficits on this passive avoidance task and that memory disturbances are at least partially responsible. Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (p<0.05), but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. In a second study, it was shown that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated administration (1 week) of the piracetam/choline combination was superior to acute injections. Regional determinations of choline and acetylcholine revealed interesting differences between treatments and brain area. Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine levels were much more subtle (only 6–10%). No significant changes following choline administration were observed in the hippocampus. However, piracetam alone markedly increased choline content in hippocampus (88%) and tended to decrease acetylcholine levels (19%). No measurable changes in striatum or cortex were observed following piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either drug alone, and in certain cases the effects were much less pronounced under the drug combination. These data were discussed as they relate to possible effects of choline and piracetam on cholinergic transmission and other neuronal function, and how these effects may reduce specific memory disturbances in aged subjects. The results of these studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with either drug alone and support the notion that in order to achieve substantial efficacy in aged subjects it may be necessary to reduce multiple, interactive neurochemical dysfunctions in the brain, or affect activity in more than one parameter of a deficient metabolic pathway.     

左乙拉西坦的药物定量脑电图研究

目的 采用药物定量脑电图研究左乙拉西坦对人类脑电活动的影响.方法 12名健康人(男女各6人,平均年龄26岁,平均体重62 kg,平均身高1.67 m)一次性口服左乙拉西坦1 g,分别于服药前,服药后1、1.5、2、3、4、6、7、8、12、24 h采集脑电信号,每次时程均为180 s.将脑电信号按频率分为δ(0.5～3.9 Hz),θ(4.0～7.9 Hz),α1(8.0～8.9 Hz),α2(9.0～10.9 Hz),α3(11.0～13.9 Hz),β(14.0～30.0 Hz)频段.将每次采集的脑电信号选取无伪差部分30 s分频段计算双额,双枕功率值.用Wilcoxon配对法检验药后各时间点功率与药前差异有无统计学意义.结果 服药后双额、枕部α1、β频段功率显著升高,双侧基本对称.服药后α2频段功率在双额部无明显变化;双枕以服药后6 h为界呈双峰样升高.左额部α1频段功率在服药后1.5 h(18.8950,Z=-3.059,P=0.002),右额部α1频段功率在服药后3 h(18.6150,Z=-2.981,P=0.003),左枕部α1频段功率在服药后1. 5、2、3、4 h(分别为61.0233、53.9425、47.6192和51.8250,Z=-3.059、-3.059、-2.903和-3.059,均P＜0.01),右枕部α1频段功率在服药后1、1.5、2、3 h(分别为53.5358、56.8092、50.3500和47.1733,Z=-2.903、-3.059、-3.059和-2.981,均P＜0.01),左枕部α2频段功率在服药后3 h(73.5450,Z=-3.059,P=0.002),右枕部α2频段功率在服药后1、3 h(80.6808、87.1750,Z=-2.903、-3.059,P=0.004、0.002),左额部β频段功率在服药后3 h(3.8000,Z=-3.059,P=0.002),右额部β频段功率在服药后1.5、2、3 h(分别为4.0408、4.3217和4.1050,Z=-2.903、-3.059和-3.061,均P＜0.01),左枕部β频段功率在服药后3 h(9.1408,Z=-3.059,P=0.002),右枕部β频段功率在服药后1.5、3 h(分别为8.9267和9.3033,Z=-2.981、-2.981,均P=0.003)与服药前相同电极比较,差异均有统计学意义.结论 左乙拉西坦对人类的脑电背景活动有影响,且与其他抗癫痫药不同.

Abstract：

Objective The quantitative pharmacoelectroencephalography ( QPEEG ) of many antiepileptic drugs (AEDs), such as carbamazepine, valproic acid, phenobarbital and topiramate but not levetiracetam (LEV), have been studied. This study is to investigate the effect of LEV on QPEEG. Methods One dose of LEV at l g was administrated to 12 healthy adults (6 males, average age at 26 years, average height at l.67 m). The EEG samples (of 180 seconds each) were obtained prior to and at regular intervals ( 1, 1.5, 2, 3, 4, 6, 7, 8, 12, 24 hours) after administration of LEV. The EEG activity was processed with the power spectral analysis and separated into different frequency bands. The absolute powers of both occipital and frontal lobes were calculated through 30 seconds epochs without artifacts for each recording. The statistical difference between baseline pre-drug control and each post-drug assessment was evaluated by the Wilcoxon matched-paired rank test. Results The power of α1-band and β-band increased bilaterally over both frontal and occipital lobes after the administration of LEV. There was no change of α2-band over bilateral frontal lobes, but increased in double peaks shape with the low point at the 6 hours after the administration. The power of α1-band showed the significant change after the administration at the 1.5 hours (18.8950, Z= -3.059, P=0.002) in the left front, 3 hours (18.6150, Z= -2.981, P =0.003)in the right front, 1.5, 2, 3 and 4 hours (61.0233, 53.9425, 47.6192 and 51.8250 respectively, Z =-3.059, -3.059, -2.903 and -3.059, all P ＜ 0.01 ) in the left occipital, and 1, 1.5, 2 and 3 hours (53.5358, 56.8092, 50.3500 and 47.1733 respectively, Z = -2.903, -3.059, -3.059 and -2.981,all P ＜ 0.01 ) in the right occipital. The power of α2-band showed the significant change after the administration at the 3 hours (73.5450, Z = - 3.059, P = 0.002) in the left occipital, and 1, 3 hours (80. 6808 and 87. 1750, Z = -2.903 and - 3.059, P = 0.004 and 0.002 respectively ) in the right occipital. The power of β-band showed the significant change after the administration at the 3 hours (3.8000, Z = -3.059, P = 0.002) in the left front, 1.5, 2 and 3 hours (4.0408, 4.3217 and 4. 1050,Z= -2.903, -3.059 and -3.061, all P＜0.01) in the right frontal, 3 hours (9.1408, Z= -3.059,P =0.002) in the left occipital, and 1.5, 3 hours (8.9267 and 9.3033, Z = -2.981 and -2.981, both P = 0.003) in the right occipital. Conclusions LEV can change the background activity of QPEEG. The changes are different from those of the other AEDs.     

天智颗粒治疗轻、中度阿尔茨海默病临床研究

目的评价天智颗粒治疗轻、中度阿尔茨海默病(alzheimer disease,AD)的有效性及安全性。方法选择简易智能状态量表(MMSE)轻、中度AD患者60例,随机分成治疗组和对照组各30例,治疗组给予天智颗粒联合吡拉西坦治疗,对照组给予吡拉西坦治疗,观察12周。治疗前后应用简易智能状态量表MMSE,日常生活能力量表(ADL)评价临床疗效;用不良反应量表(TESS)评定不良反应。结果观察12周,天智颗粒治疗组较对照组MMES、ADL评分明显改善(P<0.01)。治疗组天智颗粒治疗12周后较治疗前MMSE与ADL分数分别改善3.8分和8.0分(P<0.05,P<0.01)。天智颗粒治疗组不良反应轻,与吡拉西坦对照组比较2组差异无显著意义(P>0.05)。结论天智颗粒能有效治疗轻、中度AD患者,对患者的认知功能和日常生活自理能力均有改善,耐受性好,安全性高。     

复方司坦唑醇对D-半乳糖大鼠不同部位骨骼的影响

背景：司坦唑醇能提高骨质疏松患者骨密度,具有促进骨形成和抑制骨吸收作用,但目前还没有报道显示其对老年性骨质疏松的效果如何,对不同部位骨骼的影响也未见报道。 目的：通过骨形态计量学观察复方司坦唑醇对D-半乳糖大鼠骨质疏松模型不同部位骨骼的影响。 方法：将SD大鼠以数字表法随机分为正常对照组、D-半乳糖模型组、复方司坦唑醇组。除正常对照组颈背部皮下注射生理盐水外,其余两组颈背部皮下注射D-半乳糖制备骨质疏松模型。正常对照组和D-半乳糖模型组灌胃给予溶剂对照,复方司坦唑醇组灌胃给予司坦唑醇0.54 mg/(kg•d)+吡拉西坦432 mg/(kg•d),连续14周。测量胫骨上段松质骨和胫骨中段皮质骨骨组织形态计量学参数。 结果与结论：骨组织形态计量学参数显示,复方司坦唑醇可有效预防D-半乳糖对大鼠胫骨上段松质骨显微结构的破坏,抑制骨吸收,促进骨形成。复方司坦唑醇对D-半乳糖大鼠胫骨中段的皮质骨骨量丢失的作用不大,可抑制D-半乳糖大鼠皮质骨骨外膜的骨形成。