奥硝唑对映体对小鼠中枢抑制作用机制探究

【摘 要】 目的： 探讨右旋奥硝唑中枢抑制效应与脑内γ－氨基丁酸系统的关系。方法：经不同剂量右/左奥硝唑处理后使用Ｎ-Ｎ二甲基二吖啶硝酸盐(MQAE)荧光探针检测原代培养小鼠皮层神经元氯离子浓度， 并通过western blot方法检测GABAA受体亚基的表达。尾静脉注射给予右/左奥硝唑后测定小鼠高架十字迷宫行为。结果：右旋奥硝唑剂量依赖型激活小鼠皮层神经元的氯离子通道，经右旋奥硝唑处理后皮层神经元能增加GABAA受体α1亚基的水平且右旋奥硝唑有潜在的抗焦虑活性。结论: 右/左奥硝唑中枢作用不同，右旋奥硝唑较强的中枢抑制作用可能与激活GABA系统有关。     

高效液相色谱法拆分奥硝唑对映体

目的：建立奥硝唑对映体的手性拆分方法,并用于测定左旋奥硝唑原料和制剂中的右旋异构体。方法：采用高效液相色谱法,Ultron ES OVM手性柱(150mm×4.6mm,5μm,Agilent),通过考察影响分离的一些因素,最终确定拆分的最佳条件,即以20mmol[DK]?L-1醋酸钠(pH 5.4)-乙腈（98[DK]∶2）为流动相,流速为0.6mL[DK]?min-1,检测波长为320nm。结果：在此条件下,奥硝唑对映体之间的分离度为2.5,奥硝唑对映体最小检出浓度为0.1μg[DK]?mL-1。结论：所建立的方法简便、快速,可用于分离和测定左旋奥硝唑原料和制剂中的右旋异构体。     

左奥硝唑与奥硝唑治疗急性盆腔炎疗效和经济学评价的回顾性研究

摘要：目的:对比分析左奥硝唑和奥硝唑治疗急性盆腔炎的临床有效性、安全性及经济性。方法:收集2018年1月～2019年6月武汉大学人民医院妇产科诊断为急性盆腔炎的住院患者资料进行回顾性研究,根据治疗方案分为左奥硝唑联合头孢替安组(左奥硝唑组)和奥硝唑联合头孢替安组(奥硝唑组)采用1∶1病例对照方法对两组进行匹配。比较两组患者用药后的临床有效率、细菌清除率、不良反应发生率,并结合住院时间和住院费用进行药物经济学分析。结果:共成功匹配左奥硝唑组和奥硝唑组病例各50例。左奥硝唑组和奥硝唑组的临床有效率、厌氧菌清除率比较,差异无统计学意义(P>0.05)。两组患者的白细胞恢复情况、腹痛和发热改善情况等比较差异均无统计学意义(P>0.05);不良反应发生率差异也无统计学意义(P>0.05),不良反应类型为胃肠道反应和肝功能异常,未见其他不良反应。左奥硝唑组和奥硝唑组患者平均住院时间比较差异无统计学意义(P>0.05),奥硝唑组治疗方案的成本-效果比明显低于左奥硝唑组,左奥硝唑组的增量成本-效果比为316.50。结论:左奥硝唑和奥硝唑治疗急性盆腔炎均有效、安全,但奥硝唑更具有经济性,这一结论仍需进一步临床研究证实。     

左奥硝唑治疗厌氧菌感染的系统评价

摘 要 目的：系统评价左奥硝唑治疗厌氧菌感染的临床疗效及安全性，为临床合理用药提供参考。方法：计算机检索PubMed、Medline（viaOvidSP）、Cochrane Library、CNKI、WanFang Data、VIP数据库，搜集有关左奥硝唑治疗厌氧菌感染的随机对照试验（RCTs），检索时限均为建库至2018年10月1日，由两名研究人员独立交叉筛选文献，并进行质量评估和数据提取，采用RevMan 5.3软件进行Meta分析。结果：纳入16个RCTs，共计1 557例研究对象，其中左奥硝唑治疗厌氧菌感染的试验组779例，奥硝唑治疗厌氧菌感染的对照组778例。Meta分析结果显示：试验组的临床治愈率明显优于对照组，差异有统计学意义[OR=2.28，95%CI（1.60，3.25），P<0.000 01]；但腹部感染两组临床治愈率差异无统计学意义[OR=1.73，95%CI（0.76，3.96），P<0.19]。两组在细菌清除上效果相当，差异无统计学意义（P＞0.05）。试验组在消化系统不良反应、过敏反应以及白细胞减少等方面的发生率略低于对照组，但差异均无统计学意义（P＞0.05）；但在神经系统不良反应方面，试验组与对照组相比发生率较低，差异有统计学意义（P＜0.05）。在假设其他治疗方案一致的情况下，试验组的成本及成本 效果比显著高于对照组，在一定程度上增加了患者的医疗负担。结论：基于目前的临床研究，左奥硝唑治疗厌氧菌感染可提高临床治愈率，减少神经系统不良反应的发生，但鉴于临床发生的药品不良反应均为轻中度，无需针对治疗处理，停药后即可缓解或消失，且奥硝唑的成本 效果比远低于左奥硝唑，因此，临床医生综合评估患者病情后仍可考虑选用奥硝唑治疗厌氧菌感染。而对于合并消化系统、神经系统、免疫系统、恶性肿瘤等基础疾病，以及药品不良反应不耐受的患者，则可优选左奥硝唑。     

注射用左旋奥硝唑磷酸酯二钠对小鼠神经系统的影响

目的 探讨注射用左旋奥硝唑磷酸酯二钠静脉注射对ICR小鼠神经系统的影响.方法 将小鼠分为空白组、左旋奥硝唑(S-O)组、右旋奥硝唑磷酸酯二钠(R-ODP)组和左旋奥硝唑磷酸酯二钠(S-ODP)低、中、高剂量组(50、100、200 mg·kg-1);观察药物延长戊巴比妥钠致小鼠睡眠的时间、对运动及平衡能力的影响和对自发活动的影响.结果 S-ODP、S-O、R-ODP均可明显缩短小鼠的入睡潜伏期,延长睡眠时间;对小鼠的自发活动次数有一定的抑制作用;可降低小鼠转棒掉落时的转速、缩短掉落时间及经过路程.相同剂量R-ODP的以上作用明显强于S-ODP.结论 较高浓度S-ODP与巴比妥类镇静催眠药物有明显的协同作用,对小鼠自发活动及运动平衡能力也有轻微的影响,但效果弱于相同剂量的R-ODP.     

外翻肠囊法研究奥硝唑对映体在大鼠不同肠段的吸收特性

目的考察奥硝唑在大鼠各肠段的吸收特性及奥硝唑两手性对映体在大鼠不同肠段吸收的差异性。方法采用大鼠外翻肠囊法,以HPLC手性色谱柱法测定奥硝唑在不同肠段的吸收量以及S-奥硝唑及R-奥硝唑的同一肠段肠吸收量,并分别计算吸收速率常数(Ka)和表观渗透系数(P_(app)),同法考察了P-蛋白抑制剂(维拉帕米和环孢素A)对奥硝唑肠吸收特性的影响。结果奥硝唑在不同肠段吸收均呈线性,符合零级药物吸收速率,吸收趋势为空肠>回肠>结肠。在空肠段两对映体以近于1∶1的比例同时吸收,吸收速率不存在显著差异,随着供试液中奥硝唑质量浓度的上升,Ka呈线性增加(R~2>0.99),Paap基本保持不变,P-蛋白抑制剂对奥硝唑的肠吸收没有显著性影响(P>0.05)。结论奥硝唑在不同肠段的吸收有差异,空肠部位是吸收的最佳部位(P<0.05),S-奥硝唑与R-奥硝唑在肠道中吸收速率不存在显著差异,吸收以被动扩散机制为主,奥硝唑不是P-糖蛋白的底物。     

奥硝唑合剂对牙体牙髓病的治疗效果观察

目的观察并分析对牙体牙髓患者者使用奥硝唑合剂进行治疗的临床效果。方法在本院2014年6月至2016年9月接诊的牙体牙髓患者者中随机选取符合此次研究纳入标准的72例患者作为研究对象,并对如上患者实施分组治疗,对照组患者均采取常规根管治疗,观察组则使用奥硝唑合剂治疗,各36例。结果观察组临床治疗总有效率约为97.2%,较之对照提高程度明显(P<0.05)。对比两组不良反应发生概率,观察组也有显著降低(P<0.05)。结论对牙体牙髓患者者使用奥硝唑合剂进行临床治疗可在极大程度上提高该病症的临床治疗效果,并可有效降低不良反应的发生概率,提高临床治疗的安全性,故值得临床加以推广应用。     

三种左奥硝唑制剂在健康人体的生物利用度与生物等效性分析

通过报道一例静脉滴注莫西沙星及甲硝唑致剥脱性皮炎,复习了莫西沙星及甲硝唑的概况、不良反应及使用药学监护点,以引起临床医师及药师的重视,促进合理用药。     

三种左奥硝唑制剂在健康人体的生物利用度与生物等效性分析

目的比较3种国产左奥硝唑制剂在健康人体内的药代动力学,并评价3种制剂的生物等效性。方法 24名健康男性志愿者三交叉单剂量口服受试制剂左奥硝唑分散片、胶囊和参比制剂左奥硝唑片500mg后,用HPLC-UV法测定血药浓度,用DAS Ver 2.1计算其药代动力学参数并评价三者的生物等效性。结果受试制剂左奥硝唑分散片、胶囊和参比制剂左奥硝唑片的主要药代动力学参数:Cmax分别为(10.6±3.5)、(10.4±3.7)和(11.1±3.3)mg.L-1t;max分别为(0.76±0.70)、(1.35±0.80)和(0.92±0.84)ht;1/2分别为(13.2±1.4)、(12.9±1.7)和(12.3±1.9)h;AUC0→48分别为(140.7 31.3)、(149.5±28.5)和(143.2±37.2)mg.L-1.h;AUC0→∞分别为(152.6±33.4)、(162.0±31.8)和(153.7±30.1)mg.L-1.h。以AUC0→48、AUC0→∞作为评价依据,受试制剂对参比制剂的相对生物利用度F分别为(98.3±12.0)%、(99.512.1)%和(104.9±9.5)%、(106.0±10.5)%。结论左奥硝唑分散片、胶囊和参比制剂左奥硝唑片三种制剂生物等效。     

奥硝唑在小鼠睾丸组织中RP-HPLC检测方法的建立

目的建立一种测定睾丸组织中奥硝唑的RP-HPLC检测方法,用于奥硝唑在小鼠睾丸组织中的分布和消除规律研究。方法睾丸组织匀浆液样品经液-液萃取后,以甲醇-水=25∶75(v/v)为流动相,流速1.0mL.min-1,采用大连依利特ODS柱(250mm×4.6mm;i.d.,5μm)色谱柱分离,柱温30℃,紫外检测波长310nm。结果标准曲线线性范围0.1～50mg.kg-1,线性关系良好(r>0.999),定量限为0.1mg.kg-1,回收率95%以上,日内和日间变异系数均低于10%。结论该方法操作简便、灵敏、准确,适合于临床前药动学及组织分布的初步研究。     

Some Effects of Cassia italica on the Central Nervous System in Mice

This work examines some effects of the crude ethanolic extract of the medicinal plant Cassia italica, given at single oral doses of 0.25, 0.5 or 1 g kg^?1, on the central nervous system in mice. Several models of nociception have been used to examine the analgesic effect of the extract. HPLC fingerprinting of the extract was performed to ensure uniformity of the extract material used. In treated mice, the extract caused dose-related inhibition of acetic acid-induced abdominal constriction, and in the formalin test of antinociception the extract reduced formalin-induced pain in the second (late) but not in the first (early) phase of the pain. Treatment with the extract at doses of 0.5 and 1 g kg^?1 significantly increased the reaction time in the hot-plate and warm-water tail-flick tests. Naloxone was ineffective in antagonizing the analgesic effect of C. italica on tail-flick and abdominal constriction tests, possibly indicating that the effect occurs via non-opiate pathways. The C. italica extract caused slight dose-related impairment of motor control which was significant only at a dose of 1 g kg^?1. Treatment at the three doses used did not affect the rectal temperature of normothermic mice, but was effective in significantly reducing the rectal temperature of hyperthermic rats, 0.5 and 1 h (but not 6 h) after administration of the extract at doses of 0.5 and 1 g kg^?1. The extract also produced progressive diminution in the ambulatory and total activity of treated mice for up to 2 h after administration. It is concluded that the crude ethanolic extract of C. italica has CNS depressant properties, manifested as antinociception and sedation.     

Effects of 5-Fluorouracil Prodrugs on the Central Nervous System in Mice and Rats

The effects on the central nervous system (CNS) of mice and rats were determined for the 5-fluorouracil prodrugs, l-(2-tetrahydrofuranyl)-5-fluorouracil (FT), a combination of FT and uracil in a molar ratio of 1:4 (UFT), and l-hexylcarbamoyl-5-fluorouracil (HCFU). Both FT and UFT failed to produce a significant prolongation of hexobarital sleeping time in mice, while HCFU, at the same dose levels, caused a significant (P < 0.01) prolongation of hexo-barbital sleep. FT, UFT, and HCFU produced a slight suppression of coordinating ability in mice, but the effect of HCFU was more pronounced than that of FT and UFT. There were no significant changes in 5-hydroxytryptamine contents in the cerebral cortex and only small insignificant changes of dopamine contents in the corpus striatum by any of the drugs examined. Furthermore, HCFU was more potent than FT and UFT in potentiating the actions of ethanol. These results suggest that HCFU is more toxic to the CNS than are FT and UFT.     

Effects of Tityustoxin on Central Nervous System

Abstract

Tityustoxin mimics many effects of electrical stimulation causing cell depolarization that increases the uptake of Na⁺ and Ca²⁺ ions and the release of acetylcholine in rat brain cortical slices and synaptosomes. Tityustoxin caused mobilization of acetylcholine from the cytoplasmic and crude vesicular fractions. The release of acetylcholine by tityustoxin is Na⁺ and Ca^{2 +} dependent and is inhibited by tetrodotoxin. Tityustoxin-stimulated release of acetylcholine is blocked by ω-Agatoxin an antagonist of P-type calcium channel. The toxin activates the voltage dependent sodium channel stimulating the turnover of inositol phosphates. Chemical groups in the cell membrane, particularly SH groups, are essential for the tityustoxin-induced release of acetylcholine. Tityustoxin increased the incorporation of ³²P into synapsin I and the effect is blocked by calmodulin inhibitors. Tityustoxin increased the release of norepinephrine, glutamate, γ-aminobutyric and excitatory aminoacids. It is concluded that tityustoxin is an important tool in studies of neurotransmitter release and signal transduction.     

Effects of Petroleum Ether Extract of Amorphophallus paeoniifolius Tuber on Central Nervous System in Mice

The central nervous system activity of the petroleum ether extract of Amorphophallus paeoniifolius tuber was examined in mice, fed normal as well as healthy conditions. The petroleum ether extract of Amorphophallus paeoniifolius tuber at the doses of 100, 300 and 1000 mg/kg showed significant central nervous system activity in mice.     

柠檬烯对小白鼠中枢神经系统的影响

目的观察柠檬烯对小鼠中枢神经系统作用。方法用Y型电刺激迷宫器，40伏特的电流电刺激小鼠足趾，观察记录柠檬烯对小鼠疼痛逐避反应时间（秒）的影响、观察柠檬烯增强颅通定对电刺激小鼠足趾的镇痛作用，记录电刺激阅电压（伏特）；观察柠檬烯拮抗戊巴比妥钠催眠作用，记录入睡时间和睡眠时间（min）。结果柠檬稀能明显抑制小鼠疼痛逃避反应时间；增强颅通定镇痛作用．提高电刺激阅电压；缩短戊巴比妥钠催眠时间。结论柠檬烯有镇痛作用和促进神经中枢雏持觉醒作用。     

The Effect and Mechanism of Oxysophoridine on Central Nervous System

Objectives To study the central pharmacological effects of oxysophoride and its basic mechanism.     

Central Nervous System Receptor Activities of Some Malaysian Plant Species

ABSTRACT

In this investigation, 185 plant samples representing more than 30 plant families collected from the Malaysian forests were assessed for their ability to inhibit specific radioligand binding to 5HT1a, GABA_B, and dopamine (D2S) receptors. For this study, 96-well microplate filtration assays were adopted, and the screening parameters including screening window factor (z factor) and z′ factor indicated that the assays adopted were robust and suitable for medium-throughput screening (MTS). z factor also indicated that data on plant extracts at 10 µg/well were more reliable compared to those obtained from 100 µg/well. Therefore, only data at 10 µg/well in duplicate were used in the determination of actives. In the preliminary screen, 23 plant extracts were found to show activity (50% or higher level of inhibition over the mean of all samples for a given plate) in either one or both of the duplicates. Of these, seven were reconfirmed to be active on 5HT1a receptor in the hit confirmation. The active plant extracts were isolated from Popowia odoardoi. Diels (Annonaceae) (leaf and stem), Artabotrys roseus. Boerl. (Annonaceae) (bark), Litsea elliptibacea. Merr. (Lauraceae) (bark), Decaspermum fruticosum. Forst. (Myrtaceae) (bark), Dyera costulata. (Miq.) Hook. f. (Apocynaceae) (leaf), and Irvingia malayana. Oliv. (Simaroubaceae) (leaf). However, none of the plant extracts tested were active on either GABA_B or D2S receptors.     

Combined Effects of Xylene and Alcohol on the Central Nervous System

Abstract Ten healthy male students were exposed to m-xylene alone at concentrations of about 6 and 11.5 μmol/l and given a single dose of alcohol (0.4 and 0.8 g/kg) prior to exposure. The effects of these xylene concentrations and alcohol doses, as well as the combined effects of the two xylene concentrations with the higher alcohol dose on psychophysiological functions, such as body balance and reaction time, were assessed. Xylene alone did not significantly impair these functions, although there was a tendency towards impairment by the exposure to the higher xylene concentration. The impairment caused by alcohol alone was dose-dependent and exceeded that caused by xylene alone. The deleterious effects of xylene combined with alcohol were usually additive, although antagonism of alcohol effects on body balance by the higher xylene concentration was observed. The effects were pharmacodynamic rather than pharmacokinetic in nature.     

Pharmacokinetic-Pharmacodynamic Modelling of Zopiclone Effects on Human Central Nervous System

Abstract: The present data shows the pharmacokinetics and concentration-effect relationship of a single 7.5 mg oral dose of zopiclone in ten healthy volunteers. Plasma concentrations and effects of zopiclone on central nervous system as quantified by changes in saccadic peak velocity and digit symbol substitution test were measured for 17 hr after ingestion of zopiclone. Pharmacokinetics was described with a linear one-compartment open model. Maximum effects preceded peak plasma zopiclone concentrations causing a clockwise hysteresis, i.e. proteresis, in concentration versus effect loops. Therefore, pharmacodynamics was described both with a tolerance model and a model with distributional pseudo-tolerance where the concentration in the blood sampling site is assumed to equilibrate slower with arterial blood than the site of action of zopiclone. Both models related the changes in pharmacodynamics linearly to changes in zopiclone concentrations. The median (range) values for clearance, volume of distribution and elimination half-life were 21 (15-53) L/hr, 132 (58-161) L and 3.4 (1.7-5.7) hr, respectively. Both pharmacodynamic models were able to describe the relationship between zopiclone concentrations and changes in psychomotor performance equally well. However, because the pharmacodynamics of zopiclone were studied in a non-steady-state situation, the mechanism for proteresis, i.e. true tolerance versus distributional pseudotolerance cannot be identified.