Piracetam treatment in patients with cognitive impairment

Piracetam is a cognitive-enhancing agent that is used for the treatment of cognitive impairments of various etiologies. Little is known about its side effect profile, especially in those with psychiatric illness. We herewith present two cases with cognitive impairment who had contrasting responses to piracetam. One of them with organic amnestic syndrome had significant improvement, whereas the other who had an organic personality change as well as a family history of mental illness had significant worsening of behavioral problems after piracetam was introduced. This report highlights the need for caution in the use of piracetam, especially in those with past or family history of psychiatric illness.     

多中心双盲、随机、安慰剂对照评价左乙拉西坦添加治疗难治性部分性癫(癎)发作的疗效及安全性

目的 评价左乙拉西坦(LEV)添加用药治疗难治性部分性癫(癎)发作的临床疗效及安全性.方法 随机、双盲、安慰剂对照、多中心平行设计添加治疗,确诊为有癫(癎)部分性发作的202例癫(癎)患者,平均年龄(32.8±12.7)岁,随机分配入LEV治疗组(n=102)与安慰剂组(n=100).在回顾8周基线期的癫(癎)发作频率后,进入逐量加药期.初始用药剂量为0.5 g,每日2次,2周后增加至1.0 g,每日2次服用,4周后加量至1.5 g,每日2次,随后维持该剂量治疗12周,最后逐渐减量并转入LEV开放治疗期.主要评价指标为16周治疗期内每周癫(癎)发作频率的比较、得出药物治疗发作频率减少50%有效率、安全性和药物不良反应.结果 在16周治疗期内,LEV组每周癫(癎)发作频率明显减少,较安慰剂组减少26.8%;每周发作频率较基线期下降数在LEV组与安慰剂组的组间差异为42.2%;部分性发作频率减少50%有效率为55.9%,与安慰剂组比的OR值为3.6;有11例治疗后完全无发作,两组相比均有显著统计学意义(P＜0.001).LEV组的主要不良事件为嗜睡、头晕、无力及血小板减少,但与安慰剂组比差异无统计学意义.结论 LEV添加用药治疗成人难治性部分性癫(癎)发作,可以显著减少癫(癎)发作频率,安全性良好.     

高效液相色谱法测定吡拉西坦片的含量

目的:探讨灵敏、准确测定吡拉西坦片含量的方法.方法:采用Alltima C8柱(250.0 mm×4.6 mm,5 μm),以甲醇 水(50∶50)为流动相,流速1.0 mL•min 1,检测波长210 nm.结果:吡拉西坦的线性范围为25～150 mg•L 1,r＝1.000,平均回收率99.7%,RSD＝0.37%(n＝9).结论:该方法灵敏、准确,可作为吡拉西坦片含量测定的方法.     

胞二磷胆碱治疗早期急性脑梗死临床观察

目的：观察胞二磷胆碱用于早期急性脑梗死的临床效果。方法将91例急性脑梗死随机分为胞二磷胆碱组、依达拉奉组及吡拉西坦组,比较三组治疗效果。结果三组治疗效果无明显差异。结论胞二磷胆碱用于急性脑梗死治疗,疗效确定,不良反应发生率低,且价格低廉。     

High-shear granulation as a manufacturing method for cocrystal granules

Cocrystal formation allows the tailoring of physicochemical as well as of mechanical properties of an API. However, there is a lack of large-scale manufacturing methods of cocrystals. Therefore, the objective of this work was to examine the suitability of high-shear wet granulation as a manufacturing method for cocrystal granules on a batch scale. Furthermore, the cocrystal granules were characterized regarding their mechanical properties as well as their dissolution behavior.High-shear wet granulation was found to be a feasible manufacturing method for cocrystal granules. Cocrystal formation depended on the exposure time of the solids to the granulation liquid (water), the amount of liquid, the impeller speed of the granulator, and on the excipients (hydroxyl propylcellulose, microcrystalline cellulose, calcium hydrogenphosphate) used in the formulation. Storage stability was strongly influenced by the excipients, since in presence of calcium hydrogenphosphate, the poorly water-soluble salt calcium tartrate monohydrate was formed at high relative humidity. Interestingly, compactability was increased by cocrystal formation compared to that of the reference granules (piracetam and the respective excipients). The drug release was slightly decreased by cocrystal formation, most likely due to the lower solubility of the cocrystal. In the presence of calcium hydrogenphosphate however, no influence of cocrystal formation on either compactability or on drug release were observed, compared with the reference tablets.It was concluded that high-shear wet granulation is a valuable, however complex, manufacturing method for cocrystals. Cocrystal formation may influence compactability and drug release and thus affect drug performance and should be investigated during pre-formulation.     

Piracetam and other structurally related nootropics

Nearly three decades have now passed since the discovery of the piracetam-like nootropics, compounds which exhibit cognition-enhancing properties, but for which no commonly accepted mechanism of action has been established. This review covers clinical, pharmacokinetic, biochemical and behavioural results presented in the literature from 1965 through 1992 (407 references) of piracetam, oxiracetam, pramiracetam, etiracetam, nefiracetam, aniracetam and rolziracetam and their structural analogues. The piracetam-like nootropics are capable of achieving reversal of amnesia induced by e.g., scopolamine, electrocon-vulsive shock and hypoxia. Protection against barbiturate intoxication is observed and some benefit in clinical studies with patients suffering from mild to moderate degrees of dementia has been demonstrated. No affinity for the α₁-, α₂-, β-, muscarinic, 5-hydroxytryptamine-, dopamine, adenosine-A₁, μ-opiate, γ-aminobutyric acid (GABA) (except for nefiracetam (GABA_A)), benzodiazepine and glutamate receptors has been found. The racetams possess a very low toxicity and lack serious side effects. Increased turnover of different neurotransmitters has been observed as well as other biochemical findings e.g., inhibition of enzymes such as prolylendopeptidase. So far, no generally accepted mechanism of action has, however, emerged. We believe that the effect of the racetams is due to a potentiation of already present neurotransmission and that much evidence points in the direction of a modulated ion flux by e.g., potentiated calcium influx through non-l-type voltage-dependent calcium channels, potentiated sodium influx through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated channels or voltage-dependent channels or decreases in potassium efflux. Effects on carrier mediated ion transport are also possible.     

Effects of piracetam on the central dopaminergic transmission

Summary The effects of piracetam on dopamine metabolism in rat striatal tissue and on behavioural and biochemical effects of haloperidol were studied. Piracetam in doses 600 mg/kg and 1,000 mg/kg (i.p.) increased the levels of dopamine metabolites (homovanillic acid and 3,4-dihydroxy-phenylacetic acid) but did not influence the content of dopamine in the striatum. Piracetam (1,000 mg/kg) also increased haloperidol-induced catalepsy in rats. These results are discussed in relation to the hypothesis that some behavioural effects of piracetam can be connected with its action on dopaminergic transmission.     

大鼠微灌注脑复康对穿梭行为及脑代谢的影响

在40只大鼠中研究了不同剂量脑复康(20、200、300mg/g)对其穿梭行为及利用HPLC法研究了上述三种剂量对6个脑区还原型辅酶Ⅰ、黄素辅酶和生物蝶呤等物质含量的影响.结果表明:三种剂量脑复康与生理盐水组对比,穿梭行为指标在训练的后几天中其条件性躲避反应次数明显增多,NADH含量在各脑区无明显变化,20、200、300mg/g组在脑干的FAD含量显著降低.20mg/g组在尾核、小脑和脑干的生物蝶呤含量显著降低.     

奥拉西坦胶囊治疗颅脑外伤的临床评价

目的研究和评价奥拉西坦胶囊对于颅脑外伤患者的作用效果。方法对120例中度颅脑外伤患者进行随机双盲阳性药物脑复康(吡拉西坦)对照实验。实验组采用口服奥拉西坦胶囊2.4g/d,30d为一疗程。疗效评价采用MMSE量表、GCS量表、GOS量表、自觉症状评分等。结果服用奥拉西坦胶囊显效20例(33.3%),有效30例(50.0%),总有效率83.3%。实验组与对照组比较有显著性差异(P<0.05)。结论奥拉西坦胶囊是安全,有效的促智药,可以治疗颅脑外伤所导致的神经功能障碍,促进患者的功能康复,提高患者的生存质量,可以广泛地应用于临床。     

杏达莫注射液联合吡拉西坦治疗血管性痴呆42例疗效观察

目的:探讨银杏达莫注射液联合吡拉西坦治疗血管性痴呆的临床效果.方法:选择我院2009年4月～2011年4月血管性痴呆患者84例,将上述患者随机分为观察组和对照组.两组患者均根据具体情况实施降血压、控制血糖等常规对症治疗.对照组在以上基础上给予吡拉西坦治疗,每天0.2g口服,每天3次,连续服用60天.观察组在对照组用药基础上给予银杏达莫注射液30mL加入生理盐水注射液250mL中静脉滴注,15天为一个疗程,连续应用3个疗程.采用简易精神状态和长谷川痴呆量表检测两组患者治疗前后痴呆情况.结果:观察组治疗前MMSE、HDS和对照组治疗前比较,差异无统计学意义(P＞0.05);观察组治疗后MMSE、HDS分别与对照组治疗后比较,差异有统计学意义(P＜0.05).结论:银杏达莫注射液联合吡拉西坦能够显著改善血管性痴呆患者认知功能,临床效果显著,值得借鉴.