Differences in enhancing effects of zolpidem and benzodiazepine drugs on recurrent inhibition in rat hippocampal slices

It has been reported that the clinical and electroencephalographic profiles of zolpidem, a non-benzodiazepine drug which binds preferentially to the ω₁ benzodiazepine recognition sites located within the GABA_A receptor complex, are different from those of benzodiazepine drugs, which bind non-selectively to the ω₁ and ω₂ sites. In order to clarify the electrophysiological mechanism underlying the unique profile of zolpidem, the present study compared the enhancing effects of zolpidem and two benzodiazepine drugs, triazolam and diazepam, on recurrent inhibition. This inhibition was expressed as suppression of the orthodromically induced population spikes by the preceding antidromic stimulation of the alveus in the CA1 region of rat hippocampal slices. The rank order of potency for enhancing recurrent inhibition was triazolam > diazepam > zolpidem. From the present results and previously reported findings that zolpidem has a lower affinity for the ω₂ sites than diazepam while both have the same affinity for the ω₁ sites, we concluded that the hippocampal recurrent inhibition appears to be enhanced mainly by activation of the ω₂ sites, but not by that of the ω₁ sites. Furthermore, the lower potency of zolpidem for enhancing recurrent inhibition may underlie its unique profile in terms of its clinical and electroencephalographic effects. Received: 1 November 1996/Final version: 22 January 1997     

An improved and highly standardised transformation procedure allows efficient production of single and multiple targeted gene-knockouts in a moss,<Emphasis Type="Italic"> Physcomitrella patens</Emphasis>

The moss Physcomitrella patens is the only land plant known to date with highly efficient homologous recombination in its nuclear DNA, making it a unique model for plant functional genomics approaches. For high-throughput production of knockout plants, a robust transformation system based on polyethylene glycol-mediated transfection of protoplasts was developed and optimised. Both the DNA conformation and pre-culture of plants used for protoplast isolation significantly affected transformation efficiencies. Employing a newly developed PCR high-throughput method, the gene-targeting efficiency in more than 1,000 plants transformed with different cDNA-based knockout constructs was determined and analysed with regard to the length and intron/exon structure of the homologous gene locus. Different targeting constructs, each containing an identical selectable marker gene, were applied as batch DNA in a single transformation experiment and resulted in double-knockout plants. Thus, the fast and efficient generation of multiple targeted gene-knockouts is now feasible in Physcomitrella.Communicated by U. Kück     

Opiate induced feeding is not dependent on the hippocampus

It has been shown that spreading depression of the hippocampus can elicit feeding, and that several opioid peptides elicit spreading depression when injected into the hippocampus. To determine whether such depression is the primary mechanism by which opiates induce feeding, we tested the feeding effects of naloxone, an opiate antagonist, and butorphanol tartrate, a kappa-sigma agonist, on feeding in rats with and without hippocampal lesions. Naloxone tended to reduce intake approximately equally in the two groups. Similarly, the doses of butorphanol that increased intake in sham rats were equally effective in lesioned rats. It was concluded that the hippocampus is not the major structure mediating opiate-induced feeding.     

毛细管区带电泳法测定酒石酸唑吡坦片的含量及降解产物

目的 :采用毛细管区带电泳色谱法 (CZE)测定酒石酸唑吡坦的含量 ,并对其中的降解产物进行控制。方法 :采用CZE以 0 .0 3mol·L-1的磷酸盐缓冲液 (pH5 .0 )做运行液 ,运行电压 :16kV(运行电流 :35～ 4 5 μA) ;进样时间 :10s;检测波长 2 14nm。结果 :酒石酸唑吡坦在 2 5～ 2 5 0mg·L-1的范围内呈良好的线性关系 ,相关系数为r=0 .9995。平均回收率为 10 1.2 5 % (n=5 ) ,RSD为 0 .80 %。酒石酸唑吡坦与降解产物分离良好。结论 :本方法简便、快速、准确     

替米沙坦与吲哒帕胺联合应用治疗轻、中度高血压的临床疗效

目的 :评价替米沙坦与吲哒帕胺联用治疗轻、中度高血压的临床疗效与安全性。方法 :采用随机平行对照方法 ,将原发性轻、中度高血压患者 73例分成 3组。对照组 (n =2 4 )予替米沙坦 (4 0mg·d-1,qd) ;治疗组Ⅰ (n =2 5 )在服用替米沙坦 (2 0mg·d-1)基础上 ,加服吲哒帕胺 (1 2 5mg ,qd) ;治疗组Ⅱ (n =2 4 )在服用替米沙坦 (2 0mg·d-1)基础上 ,加服酒石酸美洛托尔 (2 5mg ,bid)。疗程均为 8wk。结果 :治疗 8wk后 ,治疗组Ⅰ和治疗组Ⅱ ,总有效率分别为 92 0 %和 83 3% ,前者与对照组总有效率6 2 5 %比较 ,P <0 0 5 ;后者与对照组比较 ,P >0 0 5。对照组、治疗组Ⅰ和治疗组Ⅱ不良反应发生例数分别为 1、3、4例。结论 :低剂量替米沙坦与吲哒帕胺联用治疗轻、中度高血压较单用替米沙坦降压效果好     

毛细管气相色谱法测定酒石酸托特罗定中有机溶剂的残留量

摘 要 目的： 建立毛细管气相色谱法测定酒石酸托特罗定中8种有机溶剂残留量的方法。 方法: 采用CP sil 5CB色谱柱（60.0 m×0.32 mm,5 μm）;进样口温度为200℃;FID检测器温度为250℃;载气流速为1.2 ml·min^-1;柱温120℃;顶空瓶平衡温度85℃,时间30 min,以二甲基甲酰胺 水（1∶4）混合溶液为溶解介质,测定酒石酸托特罗定中甲醇,乙醇,乙腈,丙酮,乙酸乙酯,三氯甲烷和四氢呋喃的残留量;采用HP 1色谱柱（30.0 m×0.53 mm,5 μm）,进样口温度为220℃;FID检测器温度为250℃;载气流速为3.0 ml·min^-1;柱温80℃;顶空瓶平衡温度85℃,时间30 min,以二甲亚砜 氢氧化钠溶液（17∶13）混合溶液为溶解介质,测定酒石酸托特罗定中吡啶的残留量。结果:在各色谱条件下,被测溶剂峰之间均分离良好,8种溶剂的标准曲线线性良好,相关系数均大于0.999;平均回收率为86.0%～100.2%,RSD为1.7%～3.5%(n=9);甲醇,乙醇,乙腈,丙酮,乙酸乙酯,三氯甲烷,四氢呋喃和吡啶的检测限分别为0.63,0.43,0.30,0.18,0.079,0.36,0.18,0.89 μg·ml^-1。结论: 该法适用于酒石酸托特罗定中这8种有机溶剂残留量的测定。     

Calendering as a direct shaping tool for the continuous production of fixed-dose combination products via co-extrusion

In this study calendering is used as a downstream technique to shape monolithic co-extruded fixed-dose combination products in a continuous way. Co-extrudates with a metoprolol tartrate-loaded sustained-release core and a hydrochlorothiazide-loaded immediate-release coat were produced and immediately shaped into a monolithic drug delivery system via calendering, using chilled rolls with tablet-shaped cavities. In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices. Analysis of the dosage forms using X-ray micro-computed tomography only detected small differences between the pore structure of the core of the calendered tablet and the mini-matrices. Diffusion path length was shown to be the main mechanism behind the release kinetics. Terahertz pulsed imaging visualized that adhesion between the core and coat of the calendered tablet was not complete and a gradient in coat thickness (varying from 200 to 600 μm) was observed. Modulated differential scanning calorimetry and X-ray diffraction indicated that the solid-state properties of both drugs were not affected by the calendering procedure.     

胺碘酮联合酒石酸美托洛尔治疗新发心房扑动的临床疗效观察

目的:探讨胺碘酮联合酒石酸美托洛尔治疗新发心房扑动的药理学与临床疗效。方法:将2012年11月—2013年11月南方医科大学南方医院44例新发心房扑动患者,通过随机抽签法分为治疗组和对照组各22例。对照组患者口服基础心脏病治疗药物,治疗组患者在对照组的基础上口服胺碘酮和酒石酸美托洛尔,对2组患者的临床治疗效果进行对比分析。结果:治疗后,治疗组患者总有效率为82%(18/22),高于对照组的27%(6/22),差异有统计学意义(P<0.05);2组患者心房扑动的各项指标、平均复律时间及平均无心房扑动复发时间、肾功能、肺功能等指标的差异均有统计学意义(P<0.05),治疗组优于对照组;治疗组患者住院时间及治疗费用均低于对照组,差异有统计学意义(P<0.05)。结论:胺碘酮联合酒石酸美托洛尔治疗新发心房扑动的疗效显著,可有效缩短患者住院时间。     

Efficacy and safety of Zolpidem in the treatment of insomnia disorder for one month: a meta-analysis of a randomized controlled trial

SubjectA meta-analysis of a randomized placebo-controlled trial was used to evaluate the effectiveness and safety of Zolpidem in the treatment of insomnia disorder for one month.MethodSearched from PubMed, EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials and web of science from inception to May 13, 2021. In addition, we also searched ClinicalTrials.gov trials register to obtain relevant research and related data. Include all randomized controlled trials that meet the criteria. The primary efficacy outcome were total sleep time and sleep latency. The secondary outcome was wake-time after sleep onset. And to evaluate the safety of Zolpidem in the treatment of insomnia.ResultsTotal of 6 randomized placebo-controlled trials involving 1068 patients with insomnia disorder were included in our study. Our analysis results showed that compared with placebo, zolpidem treatment for one month was more effective in increasing the total sleep time of patients with insomnia disorder, reducing sleep latency and improving sleep quality. There was no significant statistical difference between the two groups in the amount of change in the wake after sleep onset. Meanwhile, there was no significant statistical difference in adverse events between Zolpidem and placebo after one month of treatment.ConclusionOur meta-analysis showed that zolpidem is an effective and safe therapy option to treat insomnia disorder for one month. However, when using zolpidem to treat insomnia, its effect on sleep structure should be considered. In the future, large-scale clinical trials are needed to compare the effectiveness and safety of zolpidem in the treatment of insomnia from subjective and objective indicators combined with zolpidem on sleep structure.