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     

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。     

尼卡地平对大鼠杏仁核点燃效应的抑制作用(英文)

目的:探讨钙通道阻滞剂尼卡地平对大鼠杏仁核点燃的作用及机制。方法:恒定电流每日一次刺激大鼠右侧杏仁核,观察尼卡地平对杏仁核点燃发展和发作的影响,测定点燃大鼠脑内各种氨基酸神经递质的含量。结果:腹腔注射尼卡地平2mg·kg~(-1)显著延缓杏仁核点燃发展进程(P<0.01);尼卡地平2-20mg·kg~(-1)剂量依赖性抑制大鼠杏仁核点燃发作,升高发作阈值(ADT),降低Racine分级;20mg·kg~(-1)尼卡地平显著提高杏仁核点燃大鼠脑内抑制性氨基酸神经递质GABA的含量(P<0.05)。结论:尼卡地平对大鼠杏仁核点燃的发展和发作有抑制作用,其机制可能与阻断电压依赖性钙通道及增强GABA系统功能有关。     

纳洛酮等药物在大鼠杏仁核点燃模型中的作用

目的:观察纳洛酮等药物在点燃模型中的作用,探讨成瘾性药物的戒断症状与点燃模型的内在联系。方法:观察纳洛酮、可乐定、东莨菪碱、MK-801和尼卡地平对杏仁核点燃大鼠的影响,并测定点燃大鼠伏隔核(NAc)脑区的DA及其代谢产物的含量。结果:纳洛酮可易化杏仁核点燃,可乐定、东莨菪碱、MK-801和尼卡地平则可抑制杏仁核点燃发作(P<0·05)。点燃大鼠NAc区DA及其代谢产物升高(P<0·05)。结论:杏仁核点燃模型对纳洛酮等药物的反应及NAc脑区DA及其代谢产物的变化都与戒断反应的表现一致。     

不同钙拮抗药对大鼠杏仁核电刺激点燃模型的作用比较

目的 比较不同类型钙拮抗药对大鼠杏仁核电刺激点燃癫模型的作用及其机制。方法 采用恒定电流刺激大鼠右侧杏仁核制备大鼠杏仁核电刺激点燃慢性癫模型，观察不同类型的钙拮抗药对大鼠杏仁核电刺激点燃动物模型的后放电时程（ADD）和Racine’s分级的影响，并进行给药前后的自身对照。结果 不同类型钙拮抗药对大鼠杏仁核电刺激点燃癫发作的作用不同。尼莫地平40～80 mg·kg^-1 灌胃可抑制大鼠杏仁核电刺激点燃癫发作，降低Racine’s 分级（均P＜0.01）；地尔硫200 mg·kg^-1灌胃可抑制ADD（P＜0.05）,但对Racine’s 分级无影响（P＞0.05）;乙琥胺100～250 mg·kg^-1 灌胃对大鼠杏仁核电刺激点燃癫发作及Racine’s 分级均无抑制作用（均P＞0.05）；苯妥英钠20 mg·kg^-1 皮下注射可抑制大鼠杏仁核电刺激点燃发作，降低Racine’s分级（均P＜0.01）;丙戊酸钠500 mg·kg^-1 灌胃可抑制大鼠杏仁核电刺激点燃发作，降低Racine’s 分级（均P＜0.05）;桂利嗪20～60 mg·kg^-1灌胃可抑制大鼠杏仁核电刺激点燃癫发作，降低Racine’s 分级（均P＜0.01）。 结论 L型和T型钙通道可能参与癫发病机制，L型钙拮抗药尼莫地平具有抗癫点燃作用；较大剂量地尔硫可抑制ADD，其机制可能与阻滞L型电压依赖性钙通道（VDCC）有关; T型钙拮抗药乙琥胺对杏仁核癫点燃无抑制作用，杏仁核癫点燃发作或癫大发作与丘脑神经元低阈值T型钙通道无关；苯妥英钠、丙戊酸钠可抑制杏仁核点燃癫发作;苯妥英钠作用的T型钙通道不同于乙琥胺，该两药也可能通过其他机制抗癫;丙戊酸钠可能兼有乙琥胺和苯妥英钠对钙通道的抑制作用;桂利嗪的抗癫作用可能与阻滞多种类型的电压依赖性钙通道有关。     

小檗碱对2型糖尿病大鼠视网膜PPARα/δ/γ表达的影响

糖尿病视网膜病是最常见的糖尿病并发症之一，是导致失明的主要原因，因此有必要寻找新的治疗药物。给大鼠腹腔注射链脲菌素(35 mg·kg^-1) 2周后用高糖高脂饲料喂养14周，之后连续16周每天分别拌食给予小檗碱75、150及300 mg·kg^-1、非诺贝特100 mg·kg^-1和罗格列酮4 mg·kg^-1。用HE染色检查视网膜结构和免疫组化检测过氧化物酶体增殖物激活受体(PPARs) α/δ/γ的表达。结果发现，正常对照组大鼠的视网膜厚度大于其他各组，经小檗碱(150及300 mg·kg^-1)和罗格列酮(4 mg·kg^-1)的治疗能增加糖尿病大鼠视网膜的厚度，但视网膜的结构在各组间无差别；小檗碱(150及300 mg·kg^-1)和罗格列酮(4 mg·kg^-1)能明显降低糖尿病大鼠视网膜中PPARγ蛋白表达，小檗碱(150及300 mg·kg^-1)和非诺贝特(100 mg·kg^-1)能显著增加糖尿病大鼠视网膜中PPARα和PPARδ的表达。小檗碱调控视网膜PPAR α/δ/γ蛋白表达可能是其改善糖尿病视网膜病的机制之一，可能成为比罗格列酮和非诺贝特更有效的用于治疗糖尿病视网膜病的药物。     

脑5-HT1A/1B、α2受体及腺苷酸环化酶参与了胍丁胺的抗抑郁作用

为了在单胺受体及受体后腺苷酸环化酶(adenylate cyclase,AC)水平探讨胍丁胺(agmatine,AGM)抗抑郁作用的精细机制,采用小鼠悬尾实验和强迫游泳实验观察AGM抗抑郁行为改变。采用放射免疫方法测定大鼠前额皮层突触膜蛋白AC活性。结果表明,AGM(5～40 mg·kg^-1,ig)在小鼠悬尾实验和强迫游泳实验模型上均有显著抗抑郁活性。同时伍用β受体/5-HT_1A/1B受体阻断剂吲哚洛尔(pindolol, PIN, 20 mg·kg^-1, ip)、 α₂肾上腺素受体拮抗剂育亨宾(yohimbine, YOH, 5～10 mg·kg^-1, ip)或咪唑克生(idazoxan, IDA, 4 mg·kg^-1, ip)对AGM(40 mg·kg^-1, ig)的抗抑郁活性具有显著拮抗效应; 而β受体阻断剂普萘洛尔(propranolol, PRO, 5～20 mg·kg^-1, ip)或5-HT₃受体拮抗剂曲匹西隆(tropisetron, TRO, 5～40 mg·kg^-1, ip)对AGM(40 mg·kg^-1, ig)的抗抑郁活性无显著影响。AGM(0.1～6.4 μmol·L^-1)与大鼠前额皮层提取的突触膜共孵可剂量依赖地激活AC活性, 而PIN(1 μmol·L^-1)或YOH(0.25～1 μmol·L^-1)均显著拮抗AGM(6.4 μmol·L^-1)对AC的激活作用; 慢性给予大鼠AGM(10 mg·kg^-1, ig, bid)或氟西汀(fluoxetine, FLU, 10 mg·kg^-1, ig, bid) 2 w也显著增强大鼠前额皮层基础及Gpp(NH)p 预激活的AC活性。本研究表明, 调节脑内5-HT_1A/1B和α₂等受体功能, 并激活前额皮层AC可能是AGM抗抑郁活性的重要机制之一。     

葛根素固体脂质纳米粒抗肝损伤作用研究

目的 制备葛根素固体脂质纳米粒(puerarin solid lipid nanoparticles,Pue-SLN),对Pue-SLN进行体外释药考察,并探讨Pue-SLN对CCl4诱导的急性肝损伤大鼠的治疗作用。方法 采用乳化-超声分散法制备Pue-SLN。大鼠腹腔注射CCl4造成急性肝损伤模型。48只大鼠随机分成6组：正常组、模型组、甘草酸二胺阳性对照组(13.5 mg·kg^-1)、Pue-SLN高浓度组(27 mg·kg^-1)、中浓度组(13.5 mg·kg^-1)、低浓度组(6.75 mg·kg^-1)。分别测定大鼠血清中丙氨酸转移酶(ALT)、碱性磷酸酶(ALP)、天门冬氨酸转移酶(AST)的活力,肝组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)含量,计算肝脏指数,并对肝组织进行组织形态学检查。结果 Pue-SLN各剂量组均能抑制肝损伤大鼠血清中ALT、AST、ALP活性,降低肝匀浆中MDA含量,增强SOD、GSH-PX活性,改善肝组织的病理形态。结论 Pue-SLN对CCl4诱导的大鼠急性肝损伤具有治疗作用。     

Kappa-晒化卡拉胶对实验动物的抗心律失常作用

Kappa-硒化卡拉胶是一含硒有机化合物。ip 9 mg·kg^-1·d^-1×5d或单次ig 35,70,140mg·kg^-1能显著提高乌头碱致大鼠HA的阈剂量,此作用可与Na₂SeO₃ 1 mg·kg^-1·d^-1×5d ip比拟.随着Kappa-硒化卡拉胶ig剂量增加,尚可提高乌头碱所致VE,VT和VF的阈剂量。ip 9mg·kg^-1·d^-1×5 d或ig 70mg·kg^-1能提高BaCl₂致大鼠或哇巴因致豚鼠HA的阈剂量。对BaCl₂致大鼠VF或哇巴因致豚鼠VE的阈剂量,分别在ig70mg·kg^-1与140mg·kg^-1时有提高,而ipNa₂SeO₃ 1 mg·kg^-1·d^-1×5d无此明显影响。     

赛拉嗪对麻醉大鼠海马CA1区乙酰胆碱含量的影响

应用乙酰胆碱选择性微电极技术,观察到小剂量赛拉嗪(2.0和6.0mg·kg^-1)可显著增加大鼠海马CA1区ACh的含量,而大剂量赛拉嗪(10.0mg·kg^-1)及咪唑克生(0.6mg·kg^-1)则作用相反。咪唑克生虽可明显拮抗赛拉嗪的作用,但海马CA₁区ACh的含量仍显著低于正常水平。在去兰斑核的大鼠上,赛拉嗪(2.0和6.0mg·kg^-1)及咪唑克生(0.6mg·kg^-1)分别对海马CA₁区ACh的含量具有减少和增加作用,且咪唑克生拮抗赛拉嗪的作用后,海马CA₁区ACh的含量基本恢复至正常水平。结果提示,赛拉嗪对麻醉大鼠海马CA₁区ACh含量呈双相性影响,咪唑可生虽能显著拮抗赛拉嗪的作用,但海马CA₁区ACh的含量仍明显低于正常水平,可能分别与赛拉嗪和咪唑克生降低或提高中枢NE能系统的功能有关。     

东莨菪碱等对大鼠杏仁核点燃模型的影响

目的 :观察经常用于戒毒的药物东莨菪碱、可乐定和纳洛酮在杏仁核点燃模型中的作用 ,为戒毒药的开发研究寻找一种较好的药物筛选动物模型。方法 :制备大鼠杏仁核点燃模型 ,观察东莨菪碱对点燃发展及发作的影响 ,观察可乐定、纳洛酮对杏仁核点燃大鼠的影响。结果 :东莨菪碱 1 0 - 2 0mg·kg- 1 (ip)可抑制大鼠杏仁核点燃发展过程 (P <0 0 5 ) ;1 5 - 2 5mg·kg- 1 (ip)可抑制杏仁核点燃大鼠的发作 (P <0 0 5 )。可乐定 0 0 5 - 0 1mg·kg- 1 (ip)能降低点燃大鼠Racine’s分级 (P <0 0 5 )。纳洛酮对点燃模型无明显作用。结论 :东莨菪碱等经常用于戒毒的药物对点燃模型具有抑制作用 ,提示点燃模型对戒毒新药筛选可能有指导意义。     

Effect of felbamate and its combinations with conventional antiepileptics in amygdala-kindled rats

We investigated the effect of felbamate, administered singly and in combination with carbamazepine, phenobarbital, phenytoin or clonazepam, on various behavioral and electrographic correlates of seizures in amygdala-kindled rats. Felbamate (5 or 10 mg/kg) significantly increased afterdischarge threshold, shortened seizure and afterdischarge durations but remained without effect on seizure severity. Furthermore, the combination of felbamate (2.5 mg/kg) with carbamazepine (7.5 mg/kg; both drugs at their subeffective doses), was associated with the reduction in seizure severity and afterdischarge duration. In relation to the afterdischarge duration, the antiseizure potency of felbamate and carbamazepine, in combination, was comparable with that of carbamazepine (10 mg/kg) administered alone. Neither carbamazepine (7.5 and 10 mg/kg) nor felbamate (2.5-10 mg/kg) affected seizure severity, whereas the combined administration of felbamate (2.5 mg/kg) with carbamazepine (7.5 mg/kg) led to significant reduction in seizure severity from the fifth to the third stage of Racine's scale. Among the conventional antiepileptic drugs evaluated in this study, only valproate (100 mg/kg) and clonazepam (0.1 mg/kg) exerted similar action on seizure severity. However, the combinations of felbamate (2.5 mg/kg), with subeffective doses of valproate, phenobarbital, phenytoin or clonazepam, were not associated with any protective action. As blood and brain felbamate and carbamazepine concentrations were unaffected, a pharmacokinetic interaction can be excluded and a pharmacodynamic interaction concluded. These data suggest that felbamate and carbamazepine, administered in combination, may be useful in patients with drug-resistant partial epilepsy.     

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。     

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.     

Interaction of GYKI 52466, a selective non-competitive antagonist of AMPA/kainate receptors, with conventional antiepileptic drugs in amygdala-kindled seizures in rats.

GYKI 52466 [1,4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine], a non-competitive AMPA/kainate receptor antagonist, administered i.p. at the dose of 5 mg/kg, exerted a significant anticonvulsant effect, as it decreased seizure and afterdischarge durations, being ineffective at 2 mg/kg. Subsequently, GYKI 52466 (2 mg/kg) was combined with antiepileptic drugs at doses ineffective in fully kindled rats. Co-administration of GYKI 52466 with clonazepam (0.003 mg/kg i.p.) resulted in a significant reduction of seizure severity (by 20%), seizure duration (by 31%) and afterdischarge duration (by 24%). Co-injection of GYKI 52466 with valproate (75 mg/kg i.p.) also resulted in the respective 8%, 16%, and 17% reductions of the three studied seizure parameters. No protection was observed when GYKI 52466 was co-administered with carbamazepine (20 mg/kg i.p.), phenobarbital (20 mg/kg i.p.), or diphenylhydantoin (40 mg/kg i.p.). Combinations of GYKI 524662 with antiepileptic drugs did not cause any significant motor (rotarod test) or long-term memory deficits (passive avoidance task). Only GYKI 52466 administered alone at 5 mg/kg, caused a significant impairment of retention in amygdala-kindled rats. The interaction at a pharmacokinetic level, at least in case of the combination of GYKI 52466 with valproate, can be excluded because GYKI 52466 did not interfere with the free plasma level of valproate. These results give further support to the idea of a potential clinical benefits of the combined treatment of AMPA/kainate receptor antagonists with some antiepileptic drugs.     

Influence of antazoline and ketotifen on the anticonvulsant activity of conventional antiepileptics against maximal electroshock in mice.

Experimental studies have indicated that the central histaminergic system plays an important role in the inhibition of seizures through the stimulation of histamine H1 receptors. H1 receptor antagonists, including classical antiallergic drugs, occasionally may induce convulsions in healthy children and patients with epilepsy. The purpose of this study was to investigate the effects of antazoline and ketotifen (two H1 receptor antagonists) on the anticonvulsant activity of antiepileptic drugs against maximal electroshock (MES)-induced convulsions in mice. The following antiepileptic drugs were used: valproate, carbamazepine, diphenylhydantoin and phenobarbital. In addition, the effects of antiepileptic drugs alone or in combination with antazoline or ketotifen were studied on long-term memory (tested in the passive avoidance task) and motor performance (evaluated in the chimney test), acutely and after 7-day treatment with these H1 receptor antagonists. The influence of antazoline and ketotifen on the free plasma and brain levels of the antiepileptics was also evaluated. Antazoline (at 0.5 mg/kg), given acutely and after 7-day treatment, significantly diminished the electroconvulsive threshold. Similarly, ketotifen, after acute and chronic doses of 8 mg/kg markedly reduced the threshold for electroconvulsions. In both cases, antazoline and ketotifen were without effect upon this parameter at lower doses. Antazoline (0.25 mg/kg) significantly raised the ED50 value of carbamazepine against MES (both, acutely and after 7-day treatment). Furthermore antazoline (0.25 mg/kg) also reduced the anticonvulsant activity of diphenylhydantoin, but only after repeated administration, without modifying the brain and free plasma level of this drug. Moreover, valproate and phenobarbital did not change their protective activity when combined with antazoline. Ketotifen (4 mg/kg) possessed a biphasic action, acutely it enhanced the anticonvulsant action of carbamazepine and phenobarbital while, following 7-day treatment, reduced the antiseizure activity of carbamazepine. Ketotifen did not affect the free plasma or brain levels of antiepileptics tested. Only acute antazoline (0.25 mg/kg) applied with valproate impaired the performance of mice evaluated in the chimney test. Ketotifen (4 mg/kg) co-administered with conventional antiepileptic drugs impaired motor coordination in mice treated with valproate, phenobarbital or diphenylhydantoin. Acute and chronic antazoline (0.25 mg/kg) alone or in combination with antiepileptic drugs did not disturb long-term memory, tested in the passive avoidance task. Similarly, ketotifen (4 mg/kg) did not impair long-term memory, acutely and after 7-day treatment. However, valproate alone or in combination with chronic ketotifen (4 mg/kg) worsened long-term memory. The results of this study indicate that H1 receptor antagonists, crossing the blood brain barrier, should be used with caution in epileptic patients. This is because antazoline reduced the protective potential of diphenylhydantoin and carbamazepine. Also, ketotifen reduced the protection offered by carbamazepine and elevated the adverse activity of diphenylhydantoin, phenobarbital and valproate.     

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.     

Influence of SIB 1893, a selective mGluR5 receptor antagonist, on the anticonvulsant activity of conventional antiepileptic drugs in two models of experimental epilepsy

SIB 1893, a non-competitive antagonist of group I metabotropic glutamate receptor subtype 5, administered at doses ranging from 0.25 to 10 mg/kg, failed to influence pentetrazole-induced convulsions in mice. Moreover, SIB 1893 (10 and 20 mg/kg) did not affect the protective action of valproate, ethosuximide, phenobarbital and clonazepam in this test. Similarly, the mGluR5 antagonist did not modulate the antiseizure activity of carbamazepine, diphenylhydantoin and phenobarbital against maximal electroshock in mice. The combined treatment of SIB 1893 with conventional antiepileptic drugs did not lead to motor impairment. Long-term memory disturbances were observed only in the case of the combination of SIB 1893 with phenobarbital.