八种抗癫痫药物对小鼠马桑内酯惊厥、电惊厥的作用比较及对学习记忆的影响

用两种惊厥模型,通过跳台法和避暗法观察了临床常用的几种抗癲痫药抗惊厥作用,以及对学习记忆的影响。结果表明:对抗马桑内酯惊厥,以硝基安定和氯硝基安定效果最好,苯巴比妥及丙戊酸钠次之,酰胺咪嗪和芹菜甲素无效,而苯妥英钠及抗痫灵则能加重惊厥;在电惊厥模型中,以苯妥英钠和苯巴比妥效果最佳,丙戊酸钠及酰胺咪嗪次之,其它药物无效;除芹菜甲素外,其余七种药物均能削弱记忆获得。硝基安定和氯硝基安定可保护马桑内酯惊厥对记忆的损害,而硝基安定能加重电惊厥对记忆的损害。     

脑室内注射4-氨基吡啶诱发家兔惊厥

家兔icv 4-氨基吡啶(4-AP)8μg能诱发反复发作的惊厥,ECoG呈现高幅棘波。抗癫痫药苯妥英钠、苯巴比妥钠、安定均能有效控制4-AP诱发的惊厥,使ECoG棘波消失。丙戊酸钠也有一定效果。东莨菪碱、氟哌啶醇与酚妥拉明均能拮抗4-AP引起的惊厥。结果提示,4-AP诱发的惊厥可能与它促进中枢ACh;DA及NE等递质的释放有关。家兔icv 4-AP诱发的惊厥与常用的癫痫模型比较,有一定优点,可作为筛选抗癫痫药的动物模型之一。     

与抗癫癎药物相关的药物动力学相互作用

抗癫癎药临床应用的种类繁多,用的有巴比妥类的苯巴比妥,乙内酰脲类的苯妥英钠,亚氨基芪类的卡马西平、奥卡西平,琥珀酰亚胺类的乙琥胺、丙戊酸钠、丙戊酰胺,以及苯二氮(廿卓)类的地西泮、硝西泮等.     

癫痫持续状态59例急诊处理体会

目的探讨癫痫持续状态(SE)的急诊处理。方法59例SE患者首选地西泮静脉注射,对难治患者加用丙戊酸钠,清醒后改苯妥英钠口服。结果SE控制时间(从用药至症状消失)在5~60m in 36例,60~360m in 20例,大于360 m in 3例。治愈56例(94.92%),无效3例(5.08%)。结论安定联合丙戊酸钠及苯巴比妥钠治疗SE,效果较好,抢救成功率高。     

京都酚的致惊作用

京都酚为-中枢神经系统活性二肽,icv可使小鼠出现惊厥。右旋京都酚致惊活性明显强于左旋体。利血平化动物明显增强京都酚的致惊作用,对于京都酚在利血平化小鼠所引起的惊厥,L-Dopa可使之减弱。5-HTP及纳洛酮可使之增强;抗癫痫药中硝基安定、苯妥英钠和丙戊酸钠可明显延长发作潜伏期,缩短持续时间和减少发作率。     

病毒性脑膜炎引发癫痫持续状态患者的用药监护

一名病毒性脑炎继发癫痫的患者,在控制病毒感染的同时,联合运用苯妥英钠、苯巴比妥、丙戊酸钠和卡马西平以控制癫痫症状,但由于治疗期间停用丙戊酸钠和卡马西平致使癫痫症状加重。随后调整用药,在密切监测苯妥英钠和苯巴比妥血药浓度的情况下,加大这两种药物的用量,最终患者癫痫得到了控制,而且意识得到恢复。在整个治疗期间,临床药师与医师共同商讨治疗药物方案,医师听取并采纳了药师的合理用药建议。     

吸烟降低精神药物浓度

本文复习了吸烟对精神药物浓度的影响,发现吸烟显著降低氟奋乃静、氟哌啶、氯氮平、奥氮平、齐拉西酮、丙咪嗪、氯丙咪嗪、氟伏沙明、度洛西汀、米氮平、曲唑酮和拉莫三嗪血浓度;吸烟有可能降低氯丙嗪、利培酮、文拉法辛、阿普唑仑、氯羟安定、地西泮血浓度;吸烟不降低三氟啦嗪、奎硫平、阿立哌唑、阿米替林、去甲替林、氟西汀、舍曲林、帕罗西汀、西酞普兰、安非他酮、卡马西平、丙戊酸钠、加巴贲丁、碳酸锂、三唑仑、咪达唑仑、艾司唑仑、唑吡坦血浓度,现综述如下.     

吸烟降低精神药物浓度

本文复习了吸烟对精神药物浓度的影响,发现吸烟显著降低氟奋乃静、氟哌啶、氯氮平、奥氮平、齐拉西酮、丙咪嗪、氯丙咪嗪、氟伏沙明、度洛西汀、米氮平、曲唑酮和拉莫三嗪血浓度;吸烟有可能降低氯丙嗪、利培酮、文拉法辛、阿普唑仑、氯羟安定、地西泮血浓度;吸烟不降低三氟啦嗪、奎硫平、阿立哌唑、阿米替林、去甲替林、氟西汀、舍曲林、帕罗西汀、西酞普兰、安非他酮、卡马西平、丙戊酸钠、加巴贲丁、碳酸锂、三唑仑、咪达唑仑、艾司唑仑、唑吡坦血浓度,现综述如下。     

抗点燃药物对小鼠自主活动的影响

目的观察几种抗点燃药物对小鼠自主活动的影响。方法用光电法测定抗点燃药物托吡酯、唑尼沙铵、丙戊酸钠、卡马西平、苯妥英钠及尼可地尔用药后6h内各时间点小鼠自主活动敷。结果研究显示托吡酯、唑尼沙铵、丙戊酸钠（P〈0.01）和苯妥英钠（P〈0.05）可以减少小鼠的自主活动次数，而卡马西平及尼可地尔未见此作用。结论抗点燃药物托吡酯、唑尼沙铵、丙戊酸钠、苯妥英钠、卡马西平及尼可地尔时小鼠自发运动的影响不一，其中托吡酯、唑尼沙铵、丙戊酸钠和苯妥英钠有中枢镇静作用，而卡马西平及尼可地尔无此作用。     

过量奥卡西平致定向力障碍及共济失调

1例6岁男性癫痫患儿,曾先后口服苯妥英钠、拉莫三嗪、丙戊酸钠、苯巴比妥治疗,因不能规律服药致使癫痫反复发作且进行性加重,家属自行给予其口服奥卡西平300 mg、3次/d,上述症状未再发作。但40 d后出现行走不稳、反应迟钝,且癫痫症状也加重。入院诊断为癫痫,全身强直-阵挛发作,奥卡西平致定向力障碍及共济失调。停用奥卡西平,给予丙戊酸钠、还原性谷胱甘肽、维生素C,次日癫痫得到控制。第8天定向力障碍及共济失调消失,癫痫未再发作,遂出院。出院后规律服用丙戊酸钠和氯硝西泮。随访1个月,未再出现癫痫发作、定向力障碍和共济失调。     

Effects of antiepileptic drugs, calcium channel blockers and other compounds on seizures induced by activation of voltage-dependent L calcium channel in DBA/2 mice.

1. The convulsant activity of the calcium voltage L-channel agonist Bay k 8644 was studied in genetically epilepsy prone DBA/2 mice. 2. Seizures were induced by intracerebroventricular injection of Bay k 8644. 3. These seizures were reversed by some calcium channel blockers such as dihydropyridines, some excitatory amino acid antagonists such as 2-amino-7-phosphonoeptanoate and CPPene, 2-chloro-adenosine, some anticonvulsant drugs such as magnesium valproate, diazepam and clonazepam and two kappa opioid agonists (U-50488H and U-54494A). 4. The remaining antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and trimethadione) were ineffective in this respect. Other anticonvulsant compounds such as dizocilpine (MK 801), ketamine and drugs enhancing GABAergic transmission did not significantly affect the clonic phase of the seizures induced by Bay k 8644. 5. These results show that Bay k 8644 seizures are relatively resistant to some anticonvulsant compounds. The role of some neurotransmitters on seizures induced by Bay k 8644 is discussed.     

Effects of some calcium antagonists upon the activity of common antiepileptic compounds on sound-induced seizures in DBA/2 mice.

1. Flunarizine (2.65 mumol/kg, i.p.) and nimodipine (5.25 mumol/kg, i.p.) potentiated the anticonvulsant properties of phenytoin, phenobarbital and valproate against audiogenic seizures in DBA/2 mice. 2. Diltiazem (5.25 mumol/kg, i.p.) was able to potentiate the antiseizure activity of phenytoin but was not effective against the anticonvulsant action of phenobarbital and valproate. 3. Verapamil (5.25 mumol/kg, i.p.) was unable to potentiate the anticonvulsant properties of all antiepileptic drugs studied. 4. Bay K 8644 (1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluorophenyl)-pyridine- 5-carboxylic acid), a calcium agonist at a dose of 2.65 mumol/kg, i.p., induced a reduction of anticonvulsant potency of phenytoin, phenobarbital and valproate. 5. None of the calcium antagonists used significantly increased the plasma levels of antiepileptic compounds or significantly affected the body temperature changes induced by anticonvulsant drugs. 6. It may be concluded that some calcium antagonists enhance the anticonvulsant properties of some antiepileptic drugs against audiogenic seizures. A pharmacokinetic interaction does not seem responsible for these effects.     

丙戊酸钠添加硝西泮治疗儿童癫痫全身性发作36例

目的比较丙戊酸钠添加硝西泮和丙戊酸钠添加氯硝西泮治疗儿童癫痫全身性发作的疗效、安全性及依从性。方法选择儿童全身性发作癫痫病人59例．随机分两组分别给予丙戊酸钠添加硝西泮36例和丙戊酸钠添加氯硝西泮23例治疗，并随访观察疗效及不良反应。结果丙戊酸钠添加硝西泮治疗组与丙戊酸钠添加氯硝西泮组疗效相近，但不良反应少，性价比高。依从性好。结论丙戊酸钠添加硝西泮治疗儿童癫痫全身性发作疗效确定且价格低廉，值得在基层推广。     

Influence of vigabatrin, a novel antiepileptic drug, on the anticonvulsant activity of conventional antiepileptics in pentetrazole-induced seizures in mice

Vigabatrin is a novel antiepileptic drug, which increases GABA levels by irreversible inhibition of GABA-aminotransferase. The aim of this study was to evaluate the effects of vigabatrin on the anticonvulsant activity of valproate, ethosuximide and clonazepam against pentetrazole-induced seizures in mice. In addition, the effects of antiepileptic drugs alone or in combination with vigabatrin were studied on motor performance and long-term memory. Chemical seizures were induced by subcutaneous injection of pentetrazole at its CD(97) and defined as a clonus of the whole body with an accompanying loss of righting reflex, lasting for over 3 s. Vigabatrin inhibited the clonic pentetrazole-induced seizures and ED(30) of the drug was 879 mg/kg. Vigabatrin (at the subthreshold dose of 250 mg/kg) potentiated the protective activity of ethosuximide, reducing its ED(30) from 142 to 95 mg/kg against clonic seizures induced by pentetrazole, but simultaneously elevated its plasma level. The protective activity of valproate and clonazepam remained almost unchanged. However, vigabatrin (250 mg/kg) decreased TD(30) (50% toxic dose - corresponding to the impairment of motor coordination in 50% of the animals) of ethosuximide and clonazepam from 549 and 3.84 to 460 and 1.1 mg/kg, respectively, in the chimney test. Vigabatrin (250 mg/kg) did not influence TD(30) value of valproate in this test. Vigabatrin (at the dose of 250 mg/kg) did not impair long-term memory in combination with antiepileptics. Potentiation of the ethosuximide's protective activity was apparently due to a pharmacokinetic interaction. Consequently, no pharmacodynamic interactions between vigabatrin and the studied conventional antiepileptic drugs were evident.     

Evaluation of epileptic dogs as an animal model of human epilepsy

In 126 epileptic dogs with spontaneously recurring generalized tonic-clonic (grand mal) seizures, epidemiological aspects and the efficacy of chronic oral treatment with common antiepileptic drugs were studied. Furthermore, the pharmacokinetics of antiepileptic drugs in dogs was compared with the values known for man. As in man, idiopathic epilepsy appeared to be more common than symptomatic epilepsy in dogs. There was a preponderance of male vs. female animals. When the breeds of the epileptic dogs were compared to the distribution of breeds in the hospital population, breed-related differences in the prevalence of epilepsy were found. The highest prevalence was seen in Cocker spaniels, Miniature schnauzers, Collies and Bassets. The total prevalence of dogs with epilepsy was 0.55%. Comparison of pharmacokinetics of antiepileptic drugs showed that some drugs were suited for maintenance therapy in dogs (primidone, phenobarbital, ethosuximide, trimethadione) whereas others appeared not to be ideally suited because of their short half-lives (phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, nitrazepam). This was confirmed by the evaluation of antiepileptic drug efficacy in epileptic dogs. 46 dogs were treated with primidone at daily doses of 14-104 mg/kg for 6-60 months. During medication with primidone, effective plasma levels of its metabolite phenobarbital could be maintained. Complete control of seizures or a reduction of seizure frequency by at least 75% was achieved in 39% of the dogs at phenobarbital concentrations of 5-49 micrograms/ml. Similar figures were obtained during chronic treatment with phenobarbital at daily doses of 2.5-13 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

The spasmogenic action of potassium chloride in guinea-pig trachealis.

1 The effects of various anticonvulsant drugs were evaluated quantitatively on the development of the epileptogenic EEG, induced by the intravenous infusion of leptazol in rats anaesthetized with urethane. 2 Leptazol alone produced five distinct phases of EEG activity developing from early wave and small spike and wave activity to larger spikes which later grouped and led to full body convulsion (FBC). 3 Drugs effective in petit mal such as clonazepam (0.1 and 0.25 mg kg-1) and ethosuximide (100 and 200 mg kg-1), significantly delayed the time to FBC by prolonging the early phases of the epileptogenic EEG and delaying the appearance of spiking. 4 Drugs effective in grand mal such as sodium valproate (60 mg kg-1) and phenytoin (5 mg kg-1) significantly prolonged the time to FBC by extending the later phases of the EEG and the development and grouping of spikes. Higher doses of these compounds were without effect. Carbamazepine and phenobarbitone produced mixed effects but were generally not markedly anticonvulsant. 5 The model is sensitive to drugs effective in both petit mal and grand mal, and appears able to differentiate usefully between them.