3,4-二氯苯丙烯酰异丁胺对中枢神经系统的药理作用

7903是一种新的胡椒碱衍化物,口服给药易从胃肠道吸收,作用出现快。大鼠口服后2小时已有较强的抗MES作用,4小时作用达高峰。有效时间持续较长,48小时作用才消失。7903的抗惊厥作用较强;对多种急性和慢性实验性癫痫模型有不同程度的对抗作用,其中以对抗硫酸锌惊厥、MES和AS的作用最强;对抗戊四唑惊厥和谷氨酸钠惊厥次之。这些作用比其它胡椒碱衍化物强。此外,7903还具有镇静作用和加强其它中枢抑制药的中枢抑制作用。     

东亚钳蝎毒及其成分抗癫痫肽的抗惊厥作用

本文报道了河北产东亚钳蝎毒及从粗毒中纯化的抗癫痫肽的抗惊厥作用,本实验用咖啡因、美解眠、士的宁引起惊厥,用生理盐水作空白对照,安定做阳性对照。生理盐水对照组,惊厥发生率均达100%;严重惊厥发作率分别为50%、70%、50%;死亡率分别为40%、30%、50%,各组惊厥平均总持续时间为115min、59.5min、72min。安定对抗咖啡因惊厥的作用较小(P>O.05);但使美解眠和士的宁惊厥各项指标显著下降(P<0.05)。抗癫痫肽对抗咖啡因惊厥的作用较强,四项指标均显著下降(P<0.01),使美解眠惊厥各项指标亦明显下降(P<0.01),但稍弱;对抗士的宁惊厥的作用强度与安定相似(P<0.05)。蝎毒的抗惊厥作用较抗癫痫肽弱,与空白对照组比较差异不显著。     

实验研究天南星抗惊厥作用

目的：研究天南星在不同温度下的抗惊厥作用。方法：以对抗士的宁引起小鼠强直性惊厥及死亡的指标。比较研究了天南星不同温度提取的水溶液的抗惊厥作用。结果：发现天南星冷水浸出物对士的宁引起小鼠惊厥有明显抑制作用,且可明显降低惊厥的死亡率。     

胡椒碱衍化物的中枢药理作用研究

胡椒碱和其衍化物是一类新型的抗癫痫药,在小于TD₅₀剂量下,对电休克、戊四唑、印防已毒素、士的宁、筒箭毒碱和谷氨酸钠引起的大鼠和小鼠惊厥均有不同程度的对抗作用,并能降低动物的死亡率,可见这是一类广谱的抗惊厥药。其作用与苯妥英钠有相似之处,均能明显对抗电惊厥(MES),但又不相同,这类药物对戊四唑惊厥(Met)有效,大剂量时不引起动物惊厥。苯妥英钠与此相反。与苯巴比妥也有近似之处,抗惊谱广,但也不相同,大剂量时不引起麻醉。此外尚有镇静作用和加强其它中枢神经系统抑制药的中枢抑制作用。     

氯硝安定

【化学名】 7-硝基-5-(邻氯苯基)-1,3(2H)1,4-苯并二氮杂(艹卓)-2-酮【作用特点】本品为苯并二氮杂(艹卓)类抗惊厥药。药理作用与安定及硝基安定相似,但其抗惊厥作用比前二者强5倍,且疗效稳定。本品能较强地对抗因各种化学惊厥剂,如.戊四氮、士的宁、印防己碱,以及电休克引起的惊厥,且能     

加锡果宁的抗惊厥作用

加锡果宁(edulinine)系从芸香科植物中分离出的一种生物碱。ip或ig加锡果宁对大鼠、小鼠最大电休克(MES)有明显的对抗作用,并能对抗谷氨酸钠、戊四唑和硫代氨基脲引起的惊厥,但对印防己毒素诱发的惊厥没有明显影响。小鼠利血干预处理后,加锡果宁抗MES的ED_(50)明显增加,表明加锡果宁具有较强的抗惊厥作用,其作用可能与中枢某些递质有关。     

大鼠海马注射胍基琥珀酸引起的惊厥及对神经细胞的损害作用

大鼠海马注射微量胍基琥珀酸,可引起典型的阵挛性惊厥和癫痫样放电,用高倍显微镜进行组织学分析发现,胍基琥珀酸能广泛损伤大鼠注射侧海马CA₁部位的锥体细胞。典型的抗癫痫药苯巴比妥和苯妥英钠不能对抗上述作用,而非竞争性NMDA受体的拮抗剂氯胺酮却有对抗作用,且能预防其对海马神经细胞的损害。结果提示,胍基琥珀酸在诱发惊厥和对神经细胞的损伤方面与兴奋性氨基酸 谷氨酸的作用非常相似。同时也说明,其作用与NMDA受体有一定的关系。     

石菖蒲醇提取物的抗惊厥作用

目的：研究石菖蒲醇提取物的抗惊厥作用。方法：采用最大电休克发作（ＭＥＳ）法,士的宁惊厥法和戊四氮最小阈发作（ＭＥＴ）法,观察石菖蒲醇提取物对动物惊厥的影响。结果;石菖蒲醇提取物能明显对抗大鼠,小鼠的最大电休克发作和小鼠的戊四氮最小阈发作及士的宁的惊厥的反应。结论;石菖蒲醇提取物具有明显的抗惊厥作用。     

掌叶半夏超临界CO_2乙醇萃取物的抗惊厥作用(英文)

目的研究掌叶半夏超临界CO2乙醇萃取物(SEE-CO2 PP)对青霉素诱发惊厥的对抗作用。方法采用大鼠皮质局部定位注射青霉素诱发惊厥模型,研究SEE-CO2 PP对惊厥发作的潜伏期以及惊厥行为变化的影响,并用RM6240C型多道生理信号采集处理仪记录皮质和海马痫性放电的潜伏期、频率和痫波最高发放波幅,同时应用高效液相色谱法测定海马谷氨酸(Glu)、天冬氨酸(Asp)、甘氨酸(Gly)和γ-氨基丁酸(GABA)递质的含量。结果 SEE-CO2 PP 15和30 g·kg-1(ig)可延长青霉素诱发惊厥的潜伏期,并减弱发作强度。SEE-CO2PP能够延长痫性放电的潜伏期,减少痫性放电的频率,减小皮质和海马发放痫波的最高波幅,同时,SEE-CO2PP可以增加海马GABA的水平,对Gly,Asp和Glu水平无明显影响。结论 SEE-CO2PP可对抗青霉素诱发的惊厥行为和痫样放电,具有抗惊厥作用。     

睡宁胶囊镇静催眠作用的实验研究

目的:研究睡宁胶囊的镇静催眠作用。方法:观察睡宁胶囊对小鼠自发活动、戊巴比妥钠小鼠睡眠时间和小鼠神经运动性电惊厥的影响。结果:睡宁胶囊能显著抑制小鼠自发活动,同时有协同戊巴比妥钠作用和明显对抗小鼠"精神运动性"电惊厥发作的作用。结论:睡宁胶囊有显著的镇静催眠作用,可以用来治疗失眠。     

5-取代-1-正丁基-3-吡唑烷酮类化合物的合成及抗惊作用的构效关系

According to the quantitative structure-activity relationship studies of 3-pyrazolidinones with different substituent on positions 1 and 5 reported previously, the anticonvulsant activity is parabolically related with the total fragment constent (Fr hydrophobic parameter) of the 1 and 5 substituents of 3-pyrazolidion. The optimum Fr was about 5.6. Therefore, eleven new 5-substituted-3-pyrazolidinones have been synthesized. Pharmacological test showed that they are all potent anticonvulsant agents. Among them 1-n-butyl-5-(p-chlorophenyl)-3-pyrazolidinone was shown to be the most potent so far synthesized.     

4-取代-5-苯基-3-吡唑烷酮类化合物的合成及抗惊构效关系的研究

本文研究了4-取代-5-苯基-3-吡唑烷酮类化合物的结构与抗惊活性关系。共合成了6个3-吡唑烷酮类衍生物。其中,3-吡唑烷酮类化合物的4位引入取代基后,均使抗惊活性降低。这可能是因为3-吡唑烷酮类化合物结构中,羰基是生物活性中心,羰基的4位引入取代基会阻碍与受体的结合,使活性降低。     

Dopamine uptake inhibitory activity of novel tryptamine 5-HT1 receptor ligands

In the search for novel serotonin receptor ligands, a series of 5-thiazolyl-N,N-dimethyltryptamine derivatives was synthesized which exhibited high affinity binding to 5-HT_1A, 5-HT_1B, and 5-HT_1D receptors and the functional characteristics of receptor agonists. One member, 5-(4-anilnomethyl-2-thiazolyl)-N,N-dimethyltryptamine (CP-110,330), was found also to be a potent and selective inhibitor of dopamine uptake in rat striatal synaptosomes. This activity was confirmed by its potent displacement of [³H]N(1-[2-benzo(b)thiophenyl]cyclohexyl piperidine (BTCP) binding to the dopamine transporter in striatal membranes. A limited structure-activity study indicated that optimal dopamine uptake blocking activity was obtained when the thiazole C4 substituent consisted of phenyl with a 2-atom spacer. The potent effect of these 5-HT₁ receptor ligands on dopamine uptake can be rationalized by the observation that the flexibility of these tryptamine molecules allows the superimposition of the phenyl ring and amino group of the side chain with the corresponding moieties of tametraline, a known catecholamine uptake inhibitor of fixed conformation. A related compound, 3-(R-N-methyl-2-pyrrolidinylmethyl)-5-(4-benzyl-2-thiazolylamino)-1H-indole (CP-146,662) showed similar potent binding affinity to 5-HT₁ receptors and the dopamine transporter. Compounds with this dual serotonergic and dopaminergic activity may have utility as antidepressant agents. As potent dopamine uptake inhibitors, they may also have application in the treatment of cocaine addiction. © 1994 Wiley-Liss, Inc.     

四氢-2H-1,3,5-噻二嗪-2-硫酮类化合物的合成与抗菌活性

报道10个四氢-2H-1,3,5-噻二嗪-2-硫酮类化合物的合成与体外抗菌试验,其中7个化合物为新化合物。经元素分析、紫外光谱、红外光谱及核磁共振氢谱等确证它们的结构,并试验它们对6种细菌和2种霉菌的生物活性。结果显示此类化合物的抗菌活性显著强于临床上正在使用的磺胺嘧啶钠注射液,而稍弱于诺氟沙星注射液。对革兰氏阴性菌的抑制作用强于对革兰氏阳性菌的作用,对霉菌的活性很弱。     

Synthesis and analgesic-antiinflammatory activities of novel acylarylhydrazones with a 5-phenyl-4-R-3-pyrrolyl-acyl moiety

A new series of arylidene 5-phenyl-4-R-pyrrole-3-carbohydrazides 1a-j were prepared and evaluated for their analgesic-antiinflammatory activities. All synthesized compounds showed a significant analgesic action in mice after intraperitoneal administration at a dose of 100 microM/kg. Two of these, 1b, (4'-methylbenzylidene)-5-phenyl-1H-pyrrole-3-carbohydrazide, and 1d, (4'-chlorobenzylidene)-5-phenyl-1H-pyrrole-3-carbohydrazide, were found to be more potent as antinociceptive agents respect to dipyrone and indometacin, used as reference drugs. Among compounds 1, only 1b showed a moderate antiinflammatory effect in rats while 1d proved to be a potent non antiinflammatory analgesic.     

Pharmacogenetic correlates of pentylenetetrazol and electroconvulsive seizure thresholds in mice

Summary DBA/2J mice, susceptible to audiogenic seizures, were found to be more susceptible to pentylenetetrazol- and electrically-induced seizures than either C57BL/6J or F₁ hybrid mice, which are resistant to audiogenic seizures. Reserpine increased susceptibility to both pentylenetetrazol and electroconvulsive seizures in C57BL/6J, DBA/2J and F₁ hybrid mice. 5-hydroxytrptophan, iproniazid and amino-oxyacetic acid decreased seizure susceptibility in all groups of mice. These results were interpreted to mean that DBA/2J mice are more susceptible to seizures than C57BL/6J or F₁ hybrid mice regardless of the agents used to induce the seizures, and that levels of 5-HT, NE and GABA are important in determining seizure thresholds.This research was supported by Research Grant MH-13026 from the National Institute of Mental Health.     

Synthesis and structural studies of aza analogues of functionalized amino acids: new anticonvulsant agents

We have reported that functionalized amino acids 1 display potent anticonvulsant activities in mice and rats, and that the activity resides primarily in the D-isomer. In this study we investigated whether selectively replacing the C(2) tetrahedral atom with a trivalent nitrogen provides compounds with comparable activity. Six functionalized N(2)-substituted semicarbazides (3) were prepared. X-ray crystallographic analysis of 1-acetyl-4-benzyl-2-(thiazol-2-yl)semicarbazide (13) showed that it lost asymmetry and adopted a configuration midway between the corresponding D- and L-amino acid derivatives. Evaluation of 3 in both mice (ip) and rats (po) showed that the compounds exhibited significant anticonvulsant activities but in most cases at levels lower than their amino acid counterparts. One of the semicarbazides, 13, displayed excellent activity in mice and rats that compared favorably to that of phenytoin.     

5-取代-1-正丁基-3-吡唑烷酮类化合物的合成及抗惊作用的构效关系

1-正癸基-3-吡唑烷酮是一种新的抗惊活性物质。杜明慧、雷小平等相继合成了一系列3-吡唑烷酮类化合物,结果,1-正丙基-5-对氟苯基-3-吡唑烷酮的抗惊作用最强(EP_(50)=14.7 mg/kg)。为了继续研究1位和5位取代基对抗惊活性的影响,我们将前人合成的35个化合物(表1中化合物1～35)进行了Hansch分析得到以下方程:     

5-Lipoxygenase inhibitors: the synthesis and structure-activity relationships of a series of 1-phenyl-3-pyrazolidinones

A series of analogues of the 5-lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone, 1a) has been prepared via two complementary new synthetic methods. The reaction of various electrophiles with the dianion of 1a or with an N-silylpyrazolidinone anion gave the desired 4-substituted pyrazolidinones (Scheme I and II). A new procedure was developed for the resolution of 4-substituted pyrazolidinones (Scheme V). A regression study on 21 compounds in this series showed a correlation of increased inhibitor potency (pIC50) with increased compound lipophilicity (log P) and with an N-phenyl electronic effect as measured by the 13C NMR chemical shift parameter CNMR1' (R2 = 0.79). The most potent 5-lipoxygenase inhibitor in this series was 4-(ethylthio)-1-phenyl-3-pyrazolidinone (1n) with an IC50 of 60 nM. Another member of this series, 4-(2-methoxyethyl)-1-phenyl-3-pyrazolidinone (1f, IC50 = 0.48 microM), although less potent than 1n, was better tolerated in the whole animal relative to phenidone (1a) and also displayed good oral activity in two models of 5-lipoxygenase inhibition. On the basis of a structure-activity relationship study, a mechanism for the inhibition of 5-lipoxygenase by this class of inhibitors was proposed.     

四氢－2H－1，3，5－噻二嗪－2－硫酮类化合物的合成与抗菌活性

报道１０个四氢－２Ｈ－１，３，５－噻二嗪－２－硫酮类化合物的合成与体外抗菌试验，其中７个化合物为新化合物。经元素分析、紫外光谱、红外光谱及核磁共振氢谱等确证它们的结构，并试验它们对６种细菌和２种霉菌的生物活性。结果显示此类化合物的抗菌活性显著强于临床上正在使用的磺胺嘧啶钠注射液，而稍弱于诺氟沙星注射液。对革兰氏阴性菌的抑制作用强于对革兰氏阳性菌的作用，对霉菌的活性很弱。