二茂铁衍生物清除羟自由基的构效关系

采用化学发光法检测并比较了10种二茂铁衍生物清除羟自由基(·OH)活性,用循环伏安法研究了其电化学性质,进而探讨了取代基结构与清除·OH活性间的关系。结果表明,取代基共轭效应、诱导效应和体积都对衍生物清除·OH活性有明显影响。含共轭或吸电子取代基二茂铁衍生物,半波电位(E1/2)较高,清除·OH活性较弱;而含给电子取代基的二茂铁衍生物,E1/2较低,清除·OH活性较强。     

蝉蜕的抗惊厥作用

目的：研究蝉蜕的抗惊厥活性。方法：依次采用95％乙醇和水对蝉蜕进行提取，分别制备蝉蜕醇提物和水提物；然后采用戊四唑（PTZ）致小鼠惊厥模型对蝉蜕醇提物和水提物的抗惊厥活性进行考察。结果：蝉蜕醇提物对小鼠的惊厥发生率无影响，在4、8g／kg时可明显延长小鼠发生惊厥的潜伏期，并延长惊厥小鼠的死亡时间，降低死亡率。蝉蜕水提物4、8g／kg能显著降低小鼠惊厥发生率，且明显延长小鼠发生惊厥的潜伏期，延长惊厥小鼠的死亡时间．降低死亡率，作用强于蝉蜕醇提物实验组，但弱于苯巴比妥钠实验组。结论：蝉蜕醇提物和水提物均有抗惊厥作用，其中水提物的直接抑制作用显著，且抗惊厥作用强度明显强于醇提物。     

酸枣仁皂甙A镇静和抗惊厥作用试验

目的：考察酸枣仁皂甙（JuA)的中枢神经系统抑制作用。方法：利用新型抖笼测试系统，考察JuA积累剂量和单次剂量用药对小鼠自主活动所产生的镇静作用，同时与安定的镇静作用进行比较；并观察小鼠腹腔注射JuA后对戊四氮诱发惊厥的影响。结果：JuA积累剂量和单次剂量均可使小鼠的活动强度显著减少，静息时间显著增加，并且作用效果比较持久、平稳；但JuA对戊四氮诱发的惊厥无对抗作用。结论：JuA具有中枢神经系统镇静作用，但无抗戊四氮惊厥作用。     

5-苯基-3-吡唑烷酮类化合物的抗惊厥作用

[目的 ]研究 13个 5 苯基 3 吡唑烷酮类衍生物化合物的抗惊厥作用 .[方法 ]采用最大电惊厥法测定抗惊厥活性 ,并以苯巴比妥钠及丙戊酸钠作对照 .[结果 ]化合物 (0 1)～ (0 5)中化合物 (0 5)具有较好的抗癫痫作用 ,其ED5 0 为 46 65mg/kg ;化合物 (0 6)～ (10 )无取代基的活性最低 ;化合物 (11)～(13 )是 3类化合物中抗癫痫活性最好的化合物 ,其中化合物 (13 )的ED5 0 为 10 0 7mg/kg .[结论 ] 5 苯基 3 吡唑烷酮类衍生物均具有较好的抗癫痫作用     

Anticonvulsant activity of dapsone analogs. Electrophysiologic evaluation

BACKGROUND: In a previous study we reported that 4,4'diaminodiphenylsulfone (dapsone) has anticonvulsant activity using kainic acid (KA) model. This work shows the behavioral and electrophysiologic changes caused by systemic application of several dapsone derivatives. These derivatives include disodium salt of 4,4'-diaminodifenylsulfone N,N'-diformaldehyde sulfoxylate (I), 4,4'-diaminodiphenylsulfone N,N'-didextrose sulfonate (II), sodium dibisulfite 4,4'-biscinamilidenamindiphenyl sulfone (III), and N,N'-dimethyl-4,4'-dimethylphenylsulfone (IV), which were synthesized and purified in our laboratory. METHODS: A KA model was used to provoke limbic seizures. Limbic seizures were provoked by injection, KA, and electrophysiologic recorder at the following concentrations: 6.25 and 12.50 mg/kg of III and 6.25 and 12.50 mg/kg of IV. RESULTS: Compounds III and IV caused decrease of postdischarges; we found percentage of protection of 55.60 and 70.78%, respectively. This showed possible anticonvulsant activity of these compounds (III and IV), while I and II showed no significant changes. We also studied whether there was a dose-dependence relationship, and different doses of compound IV were evaluated (25.00, 12.50, 6.25, 3.12, and 1.62 mg/kg). We found that greatest anticonvulsant effect occurred using doses of 3.12 and 6.25 mg/kg (two of the three lowest doses). CONCLUSIONS: We concluded that IV at doses of 3.25 and 6.25 mg/kg has anticonvulsant effect because it diminished duration of the first limbic seizure induced by KA; latency of first limbic seizure crisis was also increased. Both facts demonstrated possible therapeutic application of compound IV as anticonvulsant.     

墨江蜈蚣和少棘巨蜈蚣抗惊厥药效学实验研究

对云南墨江蜈蚣(Scolopendra mojiangica Zhang et Chi)和少棘巨蜈蚣(Scolopendra subspinipes(L)Koch)进行抗惊厥药效学研究。统计学结果:前者有显著性差异(0.01相似文献   

Anticonvulsive and antioxidant effects of curcumin on pilocarpine-induced seizures in rats

Background  Curcumin, an active ingredient of turmeric with antioxidant and anti-inflammatory properties has recently been reported to have anticonvulsant effects in several animal models of epilepsy. This study aimed to investigate the effects of curcumin on the pilocarpine rat model of status epilepticus.

Methods  The effect of intraperitoneal administration of curcumin (30, 100, and 300 mg/kg) on pilocarpine-induced seizures in rats was tested. The correlation between seizure activity and hippocampal levels of nitric oxide synthase and free radicals was quantified. Whether curcumin treatment modulated these parameters was also investigated.

Results  Curcumin significantly increased seizure threshold at doses of 100 and 300 mg/kg. Rats with pilocarpine- induced seizures showed significantly elevated levels of malonaldehyde, nitric oxide synthase, and lactate dehydrogenase, but decreased levels of superoxide dismutase and glutathione compared with normal control rats. At doses of 100 and 300 mg/kg, curcumin reversed the effects of pilocarpine-induced seizures on nitric oxide synthase, lactate dehydrogenase, glutathione, and superoxide dismutase. However, curcumin did not restore the elevated malonaldehyde levels.

Conclusion  Curcumin has anticonvulsant activity in the pilocarpine rat model of seizures, and that modulation of free radicals and nitric oxide synthase may be involved in this effect.

     

3-[p(ε—取代氨基烃氧基)苯甲酰]吲哚衍生物的镇痛和抗电休克活性

5-羟色胺是吲哚类脑内神经递质,参与脑内痛觉的调节。我们曾证实次甲二氧-3-(1-β-乙基-4-甲基哌嗪)吲哚衍生物有较强的抗电休克及镇痛活性。在吲哚母核的2位氢以甲基、苯基取代或不取代,得3个系列衍生物;在吲哚母核3位上带有碱性醚链的末端氨基氮上,以不同基团取代,共得21个化合物。本文对这些化合物进行了镇痛及抗电休克活性的筛选,并对它们进行了构效关系的分析。     

1-取代苄基-5-苯基-3-吡唑烷酮衍生物的合成及抗惊厥作用

[目的]阐明1-取代苄基-5-苯基-3-吡唑烷酮衍生物的构效关系.[方法]以肉桂酸乙酯为原料,与水合肼环合反应得5-苯基-3-吡唑烷酮,再经缩合及还原得6种1-取代苄基-5-苯基-3-吡唑烷酮衍生物,采用最大电惊厥法测定其抗惊厥活性.[结果]所合成的化合物均有抗惊厥活性,其中苄基环上无取代的1-苄基-5-苯基-3-吡唑烷酮的抗惊厥作用最强.[结论]5-苯基-3-吡唑烷酮1位引入苄基可增强其抗惊厥作用.     

牛磺酸抗惊厥作用及其对脑中γ氨基丁酸、牛磺酸等含量的影响

以戊四氮（Ｐｅｎｔｅｔｒａｚｏｌ，ＰＴＺ）诱发小鼠惊厥为模型，观察单用牛磺酸及联合用苯巴比妥钠的抗惊厥作用，并测定牛磺酸对脑中γ－氨基了丁酸（ＧＡＢＡ）、牛磺酸（Ｔａｕｒｉｎｅ）、谷氨酸（Ｇｌｕｔａ－ｍａｔｅ）水平的影响。结果表明，牛磺酸可延长惊厥潜伏期，降低死亡率，牛磺酸与苯巴比妥钠合用有增强抗惊厥作用，明显降低致惊厥率。以薄层扫描色谱法测定小鼠脑中ＧＡＢＡ、牛磺酸、谷氨酸含量，结果牛磺酸可升高脑中ＧＡＢＡ和牛磺酸的水平，而对谷氨酸水平影响不大，表明牛磺酸抗惊厥作用与调节中枢谷氨酸－γ氨基丁酸轴机能有关。     

苦参碱药理作用研究进展

苦参碱(Matrine)是从苦参中提取出来的一种生物碱,已报道苦参碱具有多种药理作用,包括抗炎,免疫调节等。目前研究表明,苦参碱对中枢神经系统具有解热、镇痛、抗惊厥、稳定神经等作用;对心血管系统具有明显的负性频率和正性肌力的作用,有防治动脉粥样硬化、减轻心肌损伤的功能;对消化系统能够起到抗肝损伤、抗纤维化的效果;除此之外还具有抗肿瘤、抗肝癌的效果。本文就苦参碱近年的研究做一综述。     

1-取代苄基-N-环己基-[1,2,3]-三唑-4-甲酰胺衍生物的合成

[目的]合成具有抗癫痫作用的1取代苄基N环己基[1,2,3]三唑4甲酰胺衍生物.[方法]采用取代氯苄与叠氮钠反应生成取代苄基叠氮后,再与丙炔酸乙酯环合及酰胺化得4个1取代苄基[1,2,3]三唑4取代甲酰胺衍生物.[结果]经核磁共振氢谱、质谱及元素分析确证了所合成化合物的化学结构,为研究具有抗惊厥作用的1取代苄基三唑4甲酰胺衍生物提供了新的合成方法.     

Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice

Objective

To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid (GABA) in brain of mice in Pentylenetetrazol (PTZ) seizure models.

Methods

The anticonvulsant activity of the isolated lobeline (5, 10, 20 and 30 mg/kg, i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lobeline on brain GABA level in seizures induced by PTZ. Diazepam was used as reference anticonvulsant drugs for comparison.

Results

Isolated lobeline (10, 20 and 30 mg/kg, i.p.) significantly delayed and antagonized (P < 0.050–0.001) the onset of PTZ-induced seizures. It also antagonized strychnine induced seizures. The mortality was also prevented in the test group of animals. In biochemical evaluation, isolated lobeline (5, 10 and 20 mg/kg, i.p.) significantly increased the brain GABA level. And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model.

Conclusions

In our findings, isolated lobeline (20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures. Also a biochemical evaluation suggested significant increase in barain GABA level at 20 mg/kg i.p. of isolated lobeline. Hence, we may propose that lobeline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.     

鹅绒藤对小鼠抗惊厥作用的观察

目的：观察鹅绒藤全草水提物和氯仿提取物的抗惊厥作用。方法：采用小鼠超强电休克惊厥（MES）和戊四氮惊厥（MET）法研究提取物对实验性惊厥的影响;自主活动仪法观察提取物对小鼠自主活动的影响;转轮法测定提取物对小鼠的最小中枢神经系统毒性;采用协同阈下剂量戊巴比妥钠催眠实验,观察提取物对镇静催眠药物的协同作用。结果：鹅绒藤水提物可以对抗戊四氮惊厥（ED50=2.34g／kg）,鹅绒藤氯仿提取物在试验剂量范围内无作用。鹅绒藤氯仿提取物可以对抗最大电休克（ED50=1.34g／kg）,而水提物无对抗最大电休克的作用。两种提取物对阈下剂量戊巴比妥钠（30ms／ks,ip）的催眠效应有协同作用,水提物作用的ED50为2.36g／kg,氯仿提取物作用的ED50为0.75g/kg。两种提取物对实验小鼠自主活动有剂量依赖性抑制作用。在本实验条件下,两种提取物未呈现出中枢神经系统毒性。结论：鹅绒藤全草水提物和氯仿提取物可以对抗不同的小鼠实验性癫痫模型,鹅绒藤抗癫痫作用广泛,同时具有中枢抑制作用。     

西藏长叶松树皮乙醇提取物的抗惊厥作用

目的：研究西藏长叶松树皮乙醇提取物（alcoholic extract of bark of Pinus roxburghii Sarg．,AEPR）的抗惊厥作用。方法：用最大电休克和戊四唑诱发白化Wistar大鼠癫痫。最大电休克模型经由大鼠耳电极给予150mA电流刺激0．2S诱发癫痫,以后肢强直性伸展持续时间的变化作为结局指标衡量AEPR的抗惊厥作用,即后肢强直性伸展持续时间减少或停止。戊四唑模型大鼠经腹膜内注射戊四唑诱发肌阵挛性发作和阵发性抽搐,以痉挛发作的延迟衡量AEPR的抗惊厥作用。结果：在最大电休克惊厥模型中,AEPR剂量分别为300和500mg／kg体质量,均显著减轻所有阶段的大鼠惊厥发作（P〈O．01）;标准对照药物苯妥英钠组用量25mg／kg,能显著减轻屈曲阶段的发作（P〈0．01）,并抑制所有阶段的惊厥发作。戊四唑惊厥模型大鼠于注射戊四唑前30rain分别给予AEPR300和500mg／kg,均能显著延迟阵挛性发作（P〈0．01）。100mg／kg体质量的AEPR在戊四唑诱发的癫痫模型中没有显著的抗惊厥作用;标准对照药物地西泮4mg／kg能大幅度延迟阵挛性发作。结论：本研究提示AEPR能有效抑制普遍强直性肌阵挛和部分癫痫发作。因此,AEPR对最大电休克及戊四唑诱发的大鼠癫痫有抗惊厥作用。然而需要进一步的研究确认是AEPR中的何种成分对这种抗惊厥作用起主导作用。     

姜黄素在匹罗卡品致痫大鼠模型中抗癫痫和抗氧化作用的研究

背景 近期有研究报道姜黄素（中药姜黄中一直被认为具有抗氧化和抗炎作用的活性成分）在一些癫痫动物模型中显示出抗痫性发作作用,本课题试图探讨姜黄素在经典的匹罗卡品致痫大鼠动物模型观察其对痫性发作的影响及抗氧化作用。 方法 选用经典的匹罗卡品致痫大鼠模型,研究腹腔注射30, 100 或300 mg/kg不同剂量姜黄素对痫性发作的影响;探讨痫性发作对大鼠海马NOS和自由基的影响,不同剂量姜黄素对痫性发作后大鼠海马NOS和自由基变化的作用及与痫性发作程度的关系。 结果 100和300 mg/kg姜黄素腹腔注射增加大鼠痫性发作阈值。与正常对照组比较,匹罗卡品致痫后大鼠海马MDA含量,NOS和LDH活性明显增加,GSH含量和SOD活性显著下降,100和300 mg/kg姜黄素干预可以明显缓解痫性发作后NOS,LDH,GSH和SOD的变化程度,但是姜黄素不能缓解痫性发作后大鼠海马MDA含量的增加。 结论 本研究证实姜黄素在经典的匹罗卡品致痫大鼠模型中具有抗痫性发作作用,自由基和一氧化氮合酶可能与姜黄素的抗痫性发作作用有关。     

单侧梨状脑中间区内微量注射生理盐水对大鼠杏仁核电点燃癫痫大发作的影响

目的:探讨在大鼠梨状脑中间区微量注射生理盐水对杏仁核电点燃癫痫大发作的影响。方法:大鼠每日进行杏仁核电点燃直至达到大发作状态,随后在单侧梨状脑中间区内注射不同体积的生理盐水,并在注射后10min、30min、1d、4d、7d、10d观察大发作的发生率和阈值变化,以及持续时间的变化。结果:在同侧或对侧梨状脑中间区内注射0.1μl和0.25μl及1μl的生理盐水,均能剂量依赖性地降低癫痫大发作发生率,同时显著缩短大发作持续时间(P<0.05),而且这种作用可持续10d。同侧组在注射各个剂量生理盐水10min后即可显著升高GST(P<0.05),持续10d,而对侧组在注射剂量为0.1μl的生理盐水30min后才显著升高GST(P<0.05)。结论:单侧梨状脑中间区内注射生理盐水能够抑制大鼠杏仁核电点燃癫痫大发作,提示可能成为一种对颞叶癫痫有效的治疗手段。     

褪黑素对匹罗卡品致痫模型鼠行为改变的影响

目的　探讨褪黑素在匹罗卡品致痫大鼠模型中的抗癫痫作用及其机制。方法　采用匹罗卡品癫痫模型,观 察长期给予褪黑素对匹罗卡品致痫大鼠原发性癫痫反复发作、海马神经元丢失,苔癣纤维轴突发芽的影响。结果　给予 褪黑素后匹罗卡品致痫大鼠原发性癫痫反复发作出现的潜伏期延长,发作程度和频率均降低(P<0.01);给予褪黑素治疗 的大鼠海马CA1区Nissl染色和Timms染色评分均明显低于未用褪黑素处理的致痫大鼠(P<0.01)。结论　褪黑素能明显 降低匹罗卡品致痫大鼠原发性癫痫反复发作的频率和程度,该作用可能与褪黑素对海马神经元损伤的保护及对苔癣纤维 轴突发芽的抑制作用有关。     

Anticonvulsants in pregnancy

OBJECTIVE: To review the potential problems and their management associated with the use of anticonvulsant drugs during pregnancy. DATA SOURCES: Studies published between 1968 and 1990 assessing the effect of pregnancy on the pharmacokinetics of anticonvulsant drugs, the teratogenicity of anticonvulsants, breast feeding and anticonvulsants and use of the oral contraceptive pill in patients taking anticonvulsant medication, were reviewed. RESULTS OF DATA SYNTHESIS: In general, plasma levels fall during pregnancy and rise during the puerperium. A number of factors including possible reduced absorption, increased volume of distribution, reduced protein binding, increased clearance and noncompliance, contribute to this fall in plasma concentration. All anticonvulsants are potentially teratogenic. The incidence of fetal malformations is higher in patients treated with multiple anticonvulsant drugs and on higher dosages with higher plasma levels. Anticonvulsants are excreted in low concentrations in breast milk. All anticonvulsants except valproic acid have been associated with failure of the oral contraceptive pill. This is due to liver enzyme induction of these drugs. CONCLUSION: As plasma levels of anticonvulsants fall during pregnancy, concentrations should be monitored regularly. Due to the fall in protein binding, marginally low total plasma levels of highly protein bound drugs may not reflect reduced unbound levels, and hence an increase in dosage may not be required. In order to reduce teratogenicity, one should aim to use a single anticonvulsant drug and the lowest dosage able to achieve seizure control. In general, breast feeding is not contraindicated.     

Phytochemical screening and anticonvulsant studies of ethyl acetate fraction of Globimetula braunii on laboratory animals

ObjectiveTo investigate the phytochemical properties and the anticonvulsant potential of the ethyl acetate soluble fraction of ethanol leaf extract of Globimetula braunii, a plant used in ethnomedicine for the treatment of epilepsy.MethodsThe phytochemical screening was carried out using standard protocol while the anticonvulsant activity was studied using maximal electroshock test in chicks, pentylenetetrazole and 4-aminopyridine-induced seizures in mice.ResultsThe preliminary phytochemical screening carried out on the crude ethanol extract revealed the presence of saponins, carbohydrates, flavonoids, tannins, anthraquinones and steroids. Similarly, tannins, flavonoids and steroids/terpenes were found to be present in the ethyl acetate fraction. In the pharmacological screening, 150 mg/kg of the fraction protected 83.33% of animals against pentylenetetrazole-induced seizure in mice whereas sodium valproate a standard anti-epileptic drug offered 100% protection. In the 4-aminopyridine-induced seizure model, the fraction produced a significant (P<0.05) increase in the mean onset of seizure in unprotected animals. The fraction did not exhibit a significant activity against maximal electroshock convulsion. The median lethal dose of the fraction was found to be 1261.91 mg/kg.ConclusionsThese results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy.