镇痫灵片抗癫痫作用的实验研究

目的 :探讨镇痫灵片抗癫痫作用。方法 :采用小鼠自发活动法 ;戊巴比妥钠阈下催眠法、致惊剂 (士的宁、戊四氮 )诱发惊厥法、最小休克发作法和最大电休克发作法。结果 :镇痫灵片能明显抑制小鼠自发活动 ;增加阈下剂量戊巴比妥钠的睡眠鼠数 ;并能降低阈剂量士的宁的致惊率和小鼠戊四氮 CD50 ,提高小鼠最小休克阈值。结论 :本品具有镇静、抗惊厥作用     

白芍总甙的抗惊厥作用

采用最大电休克发作（ＭＥＳ）法、士的宁惊厥法和戊血氮最小阈发作（ＭＥＴ）法，观察白芍总甙（ＴＧＰ）对动物惊厥的影响。实验结果表明，ＴＧＰ（２０～８０ｍｇ·ｋｇ－１·ｄ－１，ｉｐ和ｉｇ×３ｄ）呈剂量依赖性对抗小鼠的ＭＥＳ。ＴＧＰ（６０～１００ｍｇ·ｋｇ－１·ｄ－１，ｉｐ）能对抗士的宁引起的小鼠和大鼠的惊厥。ＴＧＰ（４０～８０ｍｓ·ｋｇ－１·ｄ－１，ｉｐ）对小鼠的ＭＥＴ无影响。ＴＧＰ（４０～８０ｍｇ·ｋｇ－１·ｄ－１，ｉｐ）对小鼠ＭＥＳ的作用高峰时间在０．５～１．５ｈ之间。     

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。     

白芷总香豆素抗惊厥作用研究

目的:研究白芷总香豆素抗惊厥作用。方法:采用最大电休克发作模型(MES)、戊四氮和3-巯基丙酸所致的小鼠惊厥模型,研究白芷总香豆素抗惊厥作用;采用旋转棒方法,研究白芷总香豆素神经毒性作用。结果:白芷总香豆素能明显降低MES模型小鼠的惊厥发生率,明显延长戊四氮和3-巯基丙酸所致模型小鼠的惊厥潜伏期,缩短惊厥持续时间,降低小鼠的死亡率,且无明显的神经毒性作用。结论:白芷总香豆素具有抗惊厥作用。     

加巴喷丁片剂的主要药效学研究

目的　研究国产新药加巴喷丁 (GBP)的主要药效学。方法　抗惊厥试验采用最大电休克发作法 (MES)、士的宁惊厥法及戊四唑最小发作法 (MET)。结果　GBP片剂 (30～ 96 0mg·kg-1,ig)呈剂量依赖性对抗小鼠的MES及MET ;GBP片剂 (6 0～ 480mg·kg-1,ig)也能对抗士的宁引起的小鼠惊厥。结论　GBP片剂有明显的抗惊厥作用。     

石菖蒲对中枢神经系统兴奋性的有效部位研究

目的:探讨石菖蒲影响中枢神经系统兴奋性的有效部位.方法:通过小鼠阈下剂量戊巴比妥钠睡眠试验、士的宁惊厥模型试验、硫代氨基脲惊厥模型试验,观察石菖蒲系列提取部位对小鼠入睡时间、睡眠延续时间以及对2种惊厥模型小鼠的影响.结果:挥发油能明显缩短小鼠睡眠延续时间,延长2种惊厥模型的惊厥潜伏期,降低士的宁惊厥模型的惊厥率及死亡率;β 细辛醚能延长两种惊厥模型的惊厥潜伏期;其他部位除水提液外均能延长士的宁惊厥模型的惊厥潜伏期,乙醚提取部位和正丁醇提取部位能降低士的宁惊厥模型的死亡率,增加硫代氨基脲惊厥模型的死亡率.结论:石菖蒲影响中枢神经系统兴奋性的有效成分是挥发油.主要表现为兴奋醒神和抗惊厥作用.     

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。     

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     

抗痫灵抗惊厥作用的实验研究

目的探讨抗痫灵抗癫痫作用。方法采用大鼠戊四氮(PTZ)惊厥法,观察大鼠惊厥发生率,惊厥发作潜伏期及惊厥发作持续时间。结果抗痫灵能明显抑制大鼠戊四氮惊厥发生率,缩短惊厥发作持续时间,潜伏期延长,并能降低阈剂量小鼠戊四氮半数惊厥剂量(CD50)。结论本品有一定的抗惊厥作用。     

天然蝉花和人工培养品镇静镇痛作用的比较

小鼠腹腔注射天然蝉花或其人工培养品稀醇提取物能明显延长小鼠自主活动;明显延长戊巴比妥钠和水合氯醛所致小鼠的睡眠时间;提高阈下催眠剂量戊巴比妥钠的小鼠入睡率;延长中枢兴奋药士的宁和戊四氮所致小鼠惊厥的潜伏时间。经化学刺激法和热板法证明:两种样品镇痛作用明显;给正常及酵母致热大鼠腹腔注射两种样品,均具明显的降温作用。     

7-Nitroindazole, but not NG-nitro-L-arginine, enhances the anticonvulsant activity of pregabalin in the mouse maximal electroshock-induced seizure model

The objective of this study was to determine the effects of 7-nitroindazole (7NI--a preferential neuronal nitric oxide synthase (NOS) inhibitor) and NG-nitro-L-arginine (NNA--a non-selective NOS inhibitor) on the anticonvulsant action of pregabalin (PGB--a third-generation antiepileptic drug) in the maximal electroshock (MES)-induced seizure model in mice. Electroconvulsions were produced in mice by means of an alternating current (50 Hz, 500 V, 25 mA, ear-clip electrodes, 0.2 s stimulus duration, tonic hindlimb extension taken as the endpoint). The anticonvulsant action of PGB in the MES test was expressed as median effective doses (ED50 values) of the drug, protecting 50% of animals tested against MES-induced seizures. The acute adverse-effect potentials of PGB in combination with 7NI and NNA were evaluated in the chimney test (motor coordination), step-through passive avoidance task (long-term memory) and grip-strength test (skeletal muscular strength) in mice. 7NI (50 mg/kg, ip) significantly enhanced the anticonvulsant action of PGB by reducing the ED50 value of PGB from 145.0 mg/kg to 74.4 mg/kg (p<0.01). Similarly, 7NI at the lower dose of 25 mg/kg also potentiated the anticonvulsant action of PGB by lowering the ED50 value of PGB from 145.0 mg/kg to 117.9 mg/kg, although the results did not attain statistical significance. In contrast, NNA (40 mg/kg, ip) had no impact on the anticonvulsant effects of PGB. Moreover, none of the examined combinations of PGB with 7NI and NNA affected motor coordination, long-term memory and skeletal muscular strength in mice. Based on this preclinical study, one can conclude that 7NI significantly enhanced and NNA had no effect on the anticonvulsant activity of PGB against MES-induced seizures in mice.     

Anticonvulsant activity of some beta-adrenoceptor blocking agents in mice

β-Adrenoceptor blocking agents of varied chemical structure were tested for their anticonvulsant profile in mice employing the maximal electroshock seizure (MES), minimal electroshock threshold (MET) and pentylenetetrazol tests. In the MES test, propranolol, pronethalol, d-H56/28, 1-H56/28, Kö-592, PhQA33 and LB-46 abolished the tonic extensor component of the hindlimbs, while the three isomers of INPEA exhibited no protective action. In the light of observations made by other workers, these findings were interpreted to mean that: (1) adrenoceptors are not involved in mediating the anticonvulsant actions of β-adrenoceptor antagonists; and (2) ability of drugs to reduce acetylcholine concentration of the brain and their local anaesthetic property may subscribe to the anticonvulsant activity. None of the compounds elevated the MET or afforded any protection against pentylenetetrazol-induced convulsions.     

左旋组氨酸在小鼠的抗惊厥作用

目的：观察左旋组氨酸（L-His)对戊四唑（PTZ）和电刺激引起小鼠惊厥和电惊厥的实验方法，观察L-His对惊厥的影响及氯苯那敏对L-His的阻断作用。结果：L-His可拮抗PTZ，电刺激引起的惊厥，并呈现剂量依赖性，而氯苯那敏可部分拮抗L-His这种作用。结论：L-His具有抗惊厥作用。氯苯那每可部分拮抗L-His这种作用，提示L-His能通过血脑屏障进入中枢并产生抗惊厥作用。     

Synthetic cannabinoid WIN 55,212-2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock-induced seizures in mice

The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN — a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four classical antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, and valproate) in the mouse maximal electroshock seizure (MES) model. The results indicate that WIN (10 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test in mice. WIN (5 mg/kg) potentiated the anticonvulsant action of carbamazepine and valproate, but not that of phenytoin or phenobarbital in the MES test in mice. However, WIN administered alone and in combination with carbamazepine, phenytoin, phenobarbital and valproate significantly reduced muscular strength in mice in the grip-strength test. In the passive avoidance task, WIN in combination with phenobarbital, phenytoin and valproate significantly impaired long-term memory in mice. In the chimney test, only the combinations of WIN with phenobarbital and valproate significantly impaired motor coordination in mice. In conclusion, WIN enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test. However, the utmost caution is advised when combining WIN with classical antiepileptic drugs due to impairment of motor coordination and long-term memory and/or reduction of skeletal muscular strength that might appear during combined treatment.     

Antiepileptic effects of two Rho-kinase inhibitors, Y-27632 and fasudil, in mice

BACKGROUND AND PURPOSE: Rho/Rho-kinase signalling is involved in many cellular events, including some in the CNS. However, the role of this pathway in epilepsy has not yet been assessed. Therefore, we determined the effects of two Rho-kinase inhibitors, Y-27632 and fasudil, on seizures induced by pentylenetetrazole (PTZ) or maximal electroconvulsive shock (MES). EXPERIMENTAL APPROACH: Effects of Y-27632 (5-10 mg kg(-1)) and fasudil (5-25 mg kg(-1)) on duration of myoclonic jerks, clonic and tonic convulsions, tonic hindlimb extensions and percentage of tonic convulsion index, as well as recovery latency for righting reflex were investigated in mice stimulated with PTZ (65 mg kg(-1)) or MES (50 Hz, 50 mA and 0.4 s). These inhibitors were also tested on a model of kindling induced by PTZ (35 mg kg(-1), for 11 days). Membrane and cytosolic levels of RhoA protein were measured in brain homogenates from kindled mice. KEY RESULTS: Y-27632 and fasudil diminished onset of myoclonic jerks, clonic convulsions and tonic hindlimb extensions in mice given PTZ. These inhibitors suppressed the percentage of tonic convulsion index and recovery latency for righting reflex in the mice excited with MES. Western blotting demonstrated that Rho translocation to plasma membrane increased in the brain homogenates obtained from PTZ-kindled mice. However, the Rho-kinase inhibitors at the given doses did not change motor coordination of the mice. CONCLUSIONS AND IMPLICATIONS: Rho/Rho-kinase signalling may play a role in epilepsy induced by PTZ and MES. Furthermore, Rho-kinase inhibitors could be novel important antiepileptic agents.     

Studies on the anticonvulsant effect of U50488H on maximal electroshock seizure in mice

The present study was designed to investigate the effect of U50488H, a prototype non-peptide kappa opioid agonist on convulsive behaviour using a maximal electroshock (MES) seizure test in mice. An attempt was also made to explore the role of possible receptors involved. MES seizures were induced via transauricular electrodes (60 mA, 0.2 s). Seizure severity was evaluated by means of two parameters, i.e., (1). duration of tonic hindlimb extensor phase and (2). mortality due to convulsions. Intraperitoneal (i.p.) administration of U50488H dose dependently (5-20 mg/kg) decreased the hindlimb extensor phase of MES. The anticonvulsant effect of U50488H was attenuated by the general opioid antagonist, naloxone at a high dose, and by MR2266, a selective kappa antagonist, but not by naltrindole, a delta antagonist. Coadministration of gamma-aminobutyric acid (GABA)ergic drugs (diazepam, GABA, muscimol, and baclofen) and the N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK801), with U50488H augmented the anticonvulsant effect of the latter drug in mice. On the other hand, flumazenil, a central benzodiazepine (BZD) receptor antagonist, reversed the protective effect of diazepam and similarly, delta-aminovaleric acid (DAVA), a GABA(B) receptor antagonist, blocked the protective effect of baclofen, a GABA(B) agonist on the anti-MES action of U50488H. These BZD-GABAergic antagonists, namely, flumazenil or DAVA, on their own also counteracted the anti-electroshock seizure effect of U50488H given alone. However, mortality was not significantly altered in any of the above animal groups. Taken together, the findings have shown a possible role for multitude of important neurotransmitter systems, i.e., opioid (kappa), NMDA channel, GABA(A)-BZD-chloride channel complex, and GABA(B) receptors in the anticonvulsant action of U50488H.     

On the mechanism of anticonvulsant effect of tramadol in mice

The present study was conducted to examine the effects of tramadol, an atypical opioid on convulsive behaviour in maximal electroshock (MES) seizure test on mice. Moreover, an attempt was also made to investigate the role of possible receptor mechanisms involved. MES seizures were induced via transauricular electrodes (60 mA, 0.2 sec). Seizure severity was determined by (1) the duration of tonic hindlimb extensor (THE) phase and by (2) mortality due to electroconvulsions. Intraperitoneal (i.p.) administration of tramadol dose-dependently (10-50 mg/kg) decreased the duration of THE phase of MES. The anticonvulsant effect of tramadol was antagonized by the opioid antagonists, naloxone in high dose, and MR2266, a selective kappa antagonist but not by naltrindole, a delta opioid antagonist. Coadministration of either gamma-aminobutyric acid (GABA)-ergic drugs (diazepam, GABA, muscimol and baclofen) or N-methyl-D-aspartate (NMDA) receptor antagonist, MK801 with tramadol augmented the anticonvulsant effect of the latter drug. By contrast, flumazenil, a central benzodiazepine (BZD) receptor antagonist, counteracted the diazepam-induced facilitation of anti-MES effect of tramadol. Similarly, delta-aminovaleric acid (DAVA), a GABAB receptor antagonist, abolished the facilitatory effect of baclofen, a GABAB agonist on anti-MES action of tramadol. These BZD-GABAergic antagonists, flumazenil or DAVA, on their own also antagonized the anti-MES effect of tramadol administered alone. No significant effect on mortality was observed in any of the studied groups. Taken together, the current results have demonstrated a possible role for multitude of important neurotransmitter systems, i.e., opioid (kappa), GABAA-BZD receptors system, GABAB receptors and NMDA channel involvement in the antielectroshock effect of tramadol in mice.     

Possible mechanism involved in the anticonvulsant action of butorphanol in mice

The study was designed to examine the effect of butorphanol, a classical opioid on convulsive behaviour using maximal electroshock (MES) test. An attempt was also made to investigate the role of possible receptor mechanisms involved. MES seizures were induced in mice via transauricular electrodes (60 mA, 0.2 s). Seizure severity was assessed by the duration of tonic hindlimb extensor phase and mortality due to convulsions. Intraperitoneal administration of butorphanol produced a dose-dependent (0.25-2 mg/kg) protection against hindlimb extensor phase. The anticonvulsant effect of butorphanol was antagonized by all the three opioid receptor antagonists (i.e., naloxone [mu], MR2266 [kappa], and naltrindole [delta], respectively). Coadministration of gamma-aminobutyric acid (GABA)-ergic drugs (diazepam, GABA, muscimol, and baclofen) and N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK801), with butorphanol augmented the anticonvulsant action of the latter drug. In contrast, flumazenil, a central benzodiazepine (BZD) receptor antagonist, reversed the facilitatory effect of diazepam on the anti-MES effect of butorphanol. Similarly, delta-aminovaleric acid (DAVA), a GABA(B) receptor antagonist, antagonized the facilitatory effect of baclofen, a GABA(B) agonist on anti-MES action of butorphanol. These BZD-GABAergic antagonists, flumazenil or DAVA, per se also counteracted the anti-MES effect of butorphanol given alone. These data exemplify the benefits of using the MES test, which is sensitive to opioidergic compounds and distinguished convulsive behavioural changes associated with GABAergic and NMDAergic effects. Taken together, the results implicate a role for multitude of neurotransmitter systems, i.e., opioid (mu, kappa, delta), NMDA channel, BZD-GABA(A) chloride channel complex, and GABA(B) receptors in the anti-MES action of butorphanol.     

贝那替秦对最大电休克发作模型和戊四氮惊厥发作阈模型小鼠的抗惊厥作用

目的评价贝那替秦等抗胆碱药在不同惊厥模型的抗惊厥疗效,探讨其可能的作用机制。方法通过ig给予贝那替秦2~40 mg·kg-1记录最大电休克发作模型(MES)及戊四氮惊厥发作阈模型(MST)模型小鼠的未出现惊厥数。制备新生Wistar小鼠海马神经元细胞,加入贝那替秦1~100μmol·L-1,MTT检测细胞存活率。结果贝那替秦2~40 mg·kg-1在MES模型未出现惊厥数为2/10~7/10,在MST模型上未出现惊厥数为1/10~9/10均明显高于模型组(P<0.05,P<0.01),2个模型的ED50分别为12.2(4.7~53.6)mg·kg-1和12.5(7.0~25.9)mg·kg-1。贝那替秦1~100μmol·L-1能明显对抗N-甲基-D-天冬氨酸(NMDA)对海马神经元的损伤作用,细胞存活率明显增加(P<0.05)。结论贝那替秦在MES及MST惊厥模型均具明显抗惊厥作用,其作用机制可能与其对NMDA受体的拮抗作用有关。