琥珀酸对大鼠化学性点燃和杏仁核电刺激性点燃的抑制作用

目的:研究琥珀酸对大鼠戊四哇化学性点燃(kindling)发作及杏仁核电刺激点燃发作的影响及作用机制.方法:建立大鼠戊四唑化学性点燃模型和杏仁核电刺激点燃癫痫模型,测定琥珀酸对点燃发作的脑电活动及行为变化指标的影响.测定琥珀酸对GABA_A受体拮抗剂印防己毒素诱发小鼠惊厥的影响.结果:琥珀酸(100-400 mg/kg,iP)对两种点燃模型有显著抑制作用,降低发作强度和全身性发作百分率(P<0.05,P<0.01),可升高杏仁核电刺激点燃大鼠的局灶性后放电阈值(P<0.05,P<0.01),以上反应呈剂量效应关系。琥珀酸可延长印防己毒素诱发小鼠惊厥的潜伏期(P<0.05,P<0.01).结论:琥珀酸对大鼠戊四唑化学性点燃和脑杏仁核电刺激点燃发作有抑制作用,其机制可能与增强GABA_A受体功能有关.     

β肾上腺素受体拮抗剂对点燃的调控机理

目的　研究中枢β肾上腺素受体(β-AR)及其亚型在大鼠点燃模型的调控机理。方法　建立大鼠杏仁核电刺激点燃和戊四唑化学性点燃模型,观察β-AR亚型激动剂和拮抗剂对点燃和小鼠最大电休克的影响。结果　β-AR拮抗剂普萘洛尔明显延缓杏仁核点燃进程;普萘洛尔和β₁-AR拮抗剂美托洛尔均能显著抑制杏仁核点燃和化学性点燃;β₁-AR激动剂多巴酚丁胺完全逆转普萘洛尔对点燃的抑制作用,β₂-AR激动剂特布他林对普萘洛尔抑制作用无明显影响。结论　中枢β₁-AR参与杏仁核电刺激点燃和戊四唑化学性点燃的抑制作用。     

MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响(英文)

目的　在大鼠杏仁核点燃模型研究MK 80 1(地佐西平 )及其联合用药的抗癫痫作用。方法　建立大鼠杏仁核慢性电刺激点燃模型 ,测定不同剂量的MK 80 1对点燃模型各项指标的影响 ,探讨MK 80 1与其他抗癫痫药的协同作用 ,用氨基脲诱发的小鼠惊厥模型测定MK 80 1抗惊厥作用。结果　MK 80 1(0 1～ 0 2 5mg·kg- 1)可剂量依赖性抑制杏仁核点燃 ,缩短后放电时程 ,降低Racine’s分级 ;在对点燃均无明显影响的剂量下 ,MK 80 1(0 0 5mg·kg- 1)与抗癫痫药 (苯巴比妥、丙戊酸及尼卡地平 )合用可缩短后放电时程或降低Racine’s分级。MK 80 1(0 1～ 0 2 5mg·kg- 1)显著降低小鼠氨基脲诱发的发作潜伏期、惊厥发生率和死亡率。结论　MK 80 1具有抑制大鼠杏仁核点燃的作用 ,增强苯巴比妥、丙戊酸及尼卡地平的抗癫痫活性 ,为临床的合并用药提供实验依据     

丹皮总甙抗实验性癫痫的研究

目的：了解丹皮总甙是否具有抗小鼠实验性癫痫作用。方法：采用最大电惊厥（ＭＥＳ）及戊四唑、士的宁、氨基脲等化学性惊厥模型，观察丹皮总甙（ｔｏｔａｌｇｌｕｃｏｓｉｄｅｓｏｆｍｏｕｔａｎｃｏｒｔｅｒ，ＴＧＭ）对动物惊厥发作数、发作潜伏期及动物存活时间等指标的影响，从而分析ＴＧＭ抗惊厥作用及其时量效关系。结果：ＴＧＭ（６０、８０ｍｇ·ｋｇ－１ｉｐ；８０ｍｇ·ｋｇ－１ｉｇ）可减少小鼠ＭＥＳ发作数，其峰时为药后０．５～１ｈ；ＴＧＭ（６０～８０ｍｇ·ｋｇ－１ｉｇ）可延长戊四唑、士的宁、氨基脲所致小鼠惊厥的潜伏期及动物存活时间；同时ＴＧＭ（４０ｍｇ·ｋｇ－１ｉｐ）可增强苯巴比妥抗上述惊厥之作用。结论：ＴＧＭ（６０～８０ｍｇ·ｋｇ－１）呈剂量依赖性对抗小鼠ＭＥＳ及戊四唑、士的宁、氨基脲所致小鼠化学性惊厥，并可增强苯巴比妥抗惊厥作用。     

MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响

目的在大鼠杏仁核点燃模型研究MK-801(地佐西平)及其联合用药的抗癫痫作用。方法建立大鼠杏仁核慢性电刺激点燃模型,测定不同剂量的MK-801对点燃模型各项指标的影响,探讨MK-801与其他抗癫痫药的协同作用,用氨基脲诱发的小鼠惊厥模型测定MK-801抗惊厥作用。 结果MK-801(0.1～0.25 mg·kg^-1)可剂量依赖性抑制杏仁核点燃,缩短后放电时程,降低Racine's分级;在对点燃均无明显影响的剂量下,MK-801(0.05 mg·kg^-1)与抗癫痫药(苯巴比妥、丙戊酸及尼卡地平)合用可缩短后放电时程或降低Racine's分级。MK-801(0.1～0.25 mg·kg^-1)显著降低小鼠氨基脲诱发的发作潜伏期、惊厥发生率和死亡率。结论MK-801具有抑制大鼠杏仁核点燃的作用,增强苯巴比妥、丙戊酸及尼卡地平的抗癫痫活性,为临床的合并用药提供实验依据。     

国产佐匹克隆抗惊厥作用的实验研究

目的　研究国产佐匹克隆（ Ｚ Ｐ Ｌ） 的抗惊厥作用。方法　在小鼠最大电休克发作（ Ｍ Ｅ Ｓ） 和戊四唑（ Ｐ Ｔ Ｚ） 惊厥试验中记录小鼠惊厥发生率;在大鼠点燃模型中记录大鼠行为发作强度和脑后放电时程（ Ａ Ｄ Ｄ） 。结果　 Ｚ Ｐ Ｌ（２０ ,４０ ｍｇ·ｋｇ － １ ,ｉｇ） 能对抗小鼠 Ｍ Ｅ Ｓ,惊厥率分别为３５ ％ 和１５ ％ （ Ｐ＜ ００１） ;在小鼠 Ｐ Ｔ Ｚ 惊厥试验中, Ｚ Ｐ Ｌ 延长了小鼠阵挛性抽搐的潜伏期,并降低强直性发作的发生率（ Ｐ＜ ００１） ; Ｚ Ｐ Ｌ（３０ ,５０ ｍｇ·ｋｇ － １ ,ｉｇ） 减弱了点燃大鼠行为发作强度,缩短 Ａ Ｄ Ｄ（ Ｐ＜ ００１） ,尤其３０ ｍｇ·ｋｇ － １ 剂量组在无明显中枢抑制作用时就能显著地抑制点燃效应。结论　国产佐匹克隆有明显的抗惊厥作用     

托吡酯对大鼠杏仁核点燃的抑制作用

目的　在大鼠杏仁核点燃模型研究抗癫痫新药托吡酯的抗癫痫作用及其作用机制。方法　建立大鼠杏仁核电刺激点燃模型 ,并通过联合用药探讨托吡酯对点燃的作用及其可能机制 ;测定托吡酯对小鼠氨基脲惊厥的影响。结果　托吡酯 (5 0～ 2 0 0mg·kg-1,ig)可剂量依赖性抑制杏仁核点燃 (P <0 0 5 )。在对点燃均无明显影响的低剂量下 ,托吡酯与丙戊酸钠或尼卡地平合用可缩短后放电时程 (P <0 0 5 )。托吡酯 2 0 0mg·kg-1,ig ,降低小鼠氨基脲诱发的惊厥发生率和死亡率 (P <0 0 1)。结论　托吡酯能抑制杏仁核点燃 ,与丙戊酸钠、尼卡地平有协同效应 ,其机制可能与GABA能神经功能增强以及Ca2 + 拮抗有关。     

氯安定抗痫作用的耐受

<正> 氯安定是临床上抗痫作用最强的药物,然而用后却极易产生耐受。近年来公认:杏仁核点燃惊厥模型是人类复杂性部分性发作(精神运动型癫痫)继发性全身性发作的理想模型;戊四唑点燃惊厥模型是原发性全身性惊厥的理想动物模型。为了研究氯安定对抗痫作用的耐受,我们应用上述两种点燃模型,观察氯安定药物动力学     

戊四唑点燃大鼠海马、杏仁核一氧化氮合酶阳性神经元的变化

目的：探讨一氧化氮（NO）在戊四唑（PTZ）点燃发病机理中的作用,方法：每天注射PTZ建立大鼠点燃模型,运用组织化学方法观察海马,杏仁核一氧化氮合酶（NOS）阳性神经元变化,结果：点燃后海马,杏仁核内NOS阳性神经元明显增多,结论：NO促进了戊四唑点燃的形成。     

乙醇对大鼠杏仁核点燃的抑制作用

目的：研究并测定乙醇对大鼠杏仁核点燃的抑制作用.方法：建立大鼠杏仁核点燃模型,观察乙醇对点燃发展及发作的影响,并通过联合用药探讨乙醇对点燃的作用及其可能机制.结果：乙醇0.5～1.5 g&#8226;kg 1皮下注射均能升高杏仁核点燃后放电阈值,降低Racine发作强度和全身发作的百分率,抑制点燃发展进程(P＜0.01)和点燃发作(P＜0.05).在对点燃均无明显影响的低剂量下,乙醇与地西泮或苯巴比妥合用对后放电时程和Racine分级无明显影响.结论：乙醇对大鼠杏仁核点燃发作及其发展有抑制作用,但低剂量乙醇与苯巴比妥或地西泮并无协同作用.     

Phenytoin-based bivalent ligands: Design, synthesis and anticonvulsant activity

Synthesis, characterization and anticonvulsant properties of new bivalent ligands derived from phenytoin were described. Initial anticonvulsant screening was performed using maximal electroshock (MES) and pentylenetetrazole (PTZ) screens in mice. The neurotoxicity for compounds that showed significant anticonvulsant activity was determined applying the rotorod test. Most of the test compounds were found to be effective in at least one seizure model in a dose of 100 mg/kg. Compound 5e exhibited marked anticonvulsant activity in both MES and PTZ screens. The computer-aided prediction of biological activity was carried out.     

Vigabatrin as an Anticonvulsant Against Pentylenetetrazol Seizures

The anticonvulsant effects of gamma vinyl GABA (GVG) were investigated against pentylenetetrazol (PTZ) seizures, while sodium valproate (VP) was used as positive control. At 1000 and 1500 mg kg^-1 GVG was found to decrease seizure intensity either in 4 or 24 h, as effectively as VP. At 2000 mg kg^-1 GVG was found to be almost ineffective. At both doses and both time spans of drug action, seizure latency was prolonged, compared to controls and VP group.     

Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: Pharmacological and pharmacokinetic studies in rodents and the epileptic baboon

Viloxazine HCl is evaluated as an anticonvulsant in a wide range of rodent seizure models and in the epileptic baboon (Papio papio). In the maximal electroshock test, the oral ED₅₀ for abolition of tonic extension was 9 mg/kg^-1 after 30-min pretreatment (mouse) rising to 30 mg/kg^-1 after 60 min (mouse and rat). Comparable ED₅₀ values were also found for protection against tonic extension in the mouse induced by the administration of the chemical convulsants metrazole or 3-mercaptopropionic acid. In DBA/2 mice the ED₅₀ for abolition of tonic extension during sound-induced seizures was 6.8 mg/kg^-1 IP (30-min pretreatment). Pharmacokinetic studies in the mouse showed peak plasma levels to occur 30 min following oral doses, with a mean half-life of 58 min. The anticonvulsant plasma concentration was within 0.5–1 g/ml^-1. In the baboon, significant protection against photomyoclonic responses is observed 1–2 h after viloxazine (2.6 mg/kg^-1 IV), during which period the plasma concentration was again 0.5–1 g/ml^-1. After administration of approximately ten-times this latter dose level, i.e. 24 mg/kg^-1 IV, a syndrome characterised by an abnormal EEG and, in some instances, seizure activity was observed.     

Anticonvulsant and neurotoxicity profile of the rhizome of Smilax china Linn. in mice

Objective:

To study the anticonvulsant activity and neurotoxicity of ethanolic extract and ethyl acetate fraction of the rhizome of Smilax china (EESC and EAF, respectively) in mice.

Materials and Methods:

The anticonvulsant activities of EESC and EAF were studied against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice and neurotoxicity was determined using rotarod test.

Results:

The duration of hindleg extension in MES test was reduced significantly (P < 0.001) by EESC at a dose level of 400 mg/kg and EAF at both higher dose levels (200 and 400 mg/kg). In PTZ model, the seizure latency was prolonged by all the test groups.

Conclusion:

The EESC and EAF may help to control petit mal and grand mal seizures.     

天南星的抗惊厥作用

本实驗用小白鼠研究了天南星水浸剂的抗惊厥作用。以下列方法引起惊厥:(1)皮下注射士的宁;(2)皮下注射五甲烯四氮唑;(3)皮下注射咖啡因;(4)造成最大电休克发作。結果天南星水浸剂能降低士的宁、五甲烯四氮唑和咖啡因的惊厥率,但不能消除最大电休克发作。     

Synthesis, characterization & anticonvulsant activity of amide derivatives of 4-amino-1,2-naphthoquinone

In the present study, 4-amino-1,2-naphthoquinone analogues were synthesized and characterized by spectroscopic (FT-IR, ¹H NMR and ¹³C NMR) and elemental analysis. The synthesized compounds were evaluated for anticonvulsant activity by the maximal electroshock (MES) test and subcutaneous pentylenetetrazole (sc. PTZ) test, the most widely employed seizure models for early identification of anticonvulsant candidates, whereas their neurotoxicity was examined by rotarod test. Compounds were administered to animals at different concentrations (10, 20 & 40 mg/kg) by intraperitonial (i.p.) route and the % seizure protection was measured. The pharmacological results revealed that majority of compounds were effective in MES and sc. PTZ tests. Compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)butyramide (4) and N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)-3-methylbutanamide (6) were active at the dose 40 & 20 mg/kg, respectively, while compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)hexanamide (7) and 4-acetamido-N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)benzamide (10) were active at the dose 10 mg/kg and emerged as the most active compounds of the series. These compounds showed anticonvulsant effect comparable to phenytoin which was used as reference antiepileptic drug. The above-mentioned compounds have diminutive neurotoxic effects so they can move on next phase of anticonvulsant drug development.     

The effect ofN-alkyloxycarbonyl group on the anticonvulsant activities ofN-alkyloxycarbonyl-α-aminoglutarimides

In connection with the development of new anticonvulsant agents with a broad spectrum, we reported thatN-Cbz-α-aminoglutarimides, combining common structures of other anticonvulsants such as N-CO-C-N and cyclic imides in a single molecule, showed significant anticonvulsant activities in the MES (maximal electroshock seizure) and PTZ (pentylenetetrazole induced seizure) tests. In these studies, a series of (R) and (S)N-alkyloxycarbonyl-α-aminoglutarimides7a∼7e and8a∼8e, which were substituted with various alkyloxycarbonyl group instead ofCbz group, were prepared from the corresponding (R) and (S)N-Cbz-glutamic acid3 and4, and were evaluated with their anticonvulsant activities against the MES and PTZ tests, including neurotoxicity, in order to define the effect ofN-alkyloxycarbonyl group on the anticonvulsant activities ofN-alkyloxycarbonyl-α-aminoglutarimides. Among them, (S)N-4-nitrobenzyloxycarbonyl-α-amino-N-methylglutarimide8e was the most active in MES (ED₅₀=35.6 mg/kg, Pl=2.7) and PTZ tests (ED₅₀=15.6, Pl=6.1). Interestingly, (R) and (S)N-4-nitrobenzyloxycarbonyl-α-amino-N-methylglutarimide7e and8e and (R)N-phenoxycarbonyl-α-amino-N-methylglutrimide7d showed significant anticonvulsant activities in both the MES and PTZ tests and other compounds showed anticonvulsant activities in only the PTZ test. In addition, it was found that their anticonvulsant activities were dependent on their stereochemistries andN-substituted alkyloxycarbonyl groups.     

川芎嗪抗小鼠实验性癫痫的研究

目的:系统评价川芎嗪(Tetramethylpyrazine,TMP)是否具有抗小鼠实验性癫痫作用。方法:采用最大电惊厥(MES)及戊四氮、士的宁、匹罗卡品等癫痫模型。观察川芎嗪(TMP)低、中、高(200、400、800mg.kg-1)剂量对动物惊厥发作数、阵挛潜伏期及动物存活时间等指标的影响,从而分析川芎嗪抗惊厥作用及其时量关系。结果:中、高剂量(400、800mg.kg-1)川芎嗪可明显减少MES发作次数,延长戊四氮、士的宁所致小鼠阵挛潜伏期,同时延长死亡时间。高剂量川芎嗪可延长小鼠匹罗卡品癫痫模型的阵挛时间,与模型组相比,差异有统计学意义。结论:川芎嗪对癫痫有一定防治作用,并存在一定的量效关系。     

Anticonvulsant activity of ethanol extracts of Vetiveria zizanioides roots in experimental mice

?Abstract

Context: Vetiveria zizanioides Linn. (Gramineae), an aromatic plant commonly known as vetiver, is traditionally used for various ailments. Ethanol and aqueous extract of this plant found extensive use in Indian folklore medicine and used in treatment of a wide range of disorders including seizure. However, the anticonvulsant activity of this plant has not been studied.

Objective: To evaluate anticonvulsant activity of ethanol extract of V. zizanioides (EEVZ) in experimental mice.

Materials and methods: Anticonvulsant activity of EEVZ was determined by maximal electroshock stimulation (MES) and pentylenetetrazole (PTZ) in mice for 8?d experimental protocol. The extract at a dose of 100, 200 and 400?mg/kg body weight was administered once by oral route.

Results: LD₅₀ value of EEVZ in mice was found at a dose of 600?mg/kg body weight. EEVZ at a dose of 400?mg/kg significantly (p?<?0.001) reduced flexion (l5.98 to 3.73?s), extension (13.73 to 0.96?s), clonus (14.07 to 4.93?s), stupor (6.29 to 1.22?s) in the MES model. Further, it increases onset of clonic (88.25 to 708.32?s/30?min) and tonic (139.52 to 1126.39?s/30?min) in the PTZ model. In the PTZ model, 33% normal control and 83% EEVZ (100?mg/kg) animals were alive, while 100% protection was achieved in standard drug phenobarbital (20?mg/kg), EEVZ (200?mg/kg) and EEVZ (400?mg/kg) animals.

Discussion and conclusion: Findings demonstrate that V. zizanioides shows significant anticonvulsant activity in mice.