118例癫痫患者卡马西平血药浓度监测结果及影响因素分析

目的 探讨癫痫患者卡马西平（CBZ）血药浓度的影响因素,为临床合理使用提供依据。方法 选取118例规律服用卡马西平治疗的癫痫患者作为研究对象,采用高效液相色谱法（HPLC）进行血药浓度监测,分析影响卡马西平血药浓度的因素。结果 75.42%的患者服用卡马西平后血药浓度控制在4~12 μg·mL^-1之间;性别因素、年龄因素对卡马西平血药浓度的影响不明显（P＞0.05）;联合其他抗癫痫药时,无效浓度比例较高,具有统计学差异(P＜0.05)。结论 服用卡马西平后,患者卡马西平血药浓度的个体差异大,尤其是合并使用其他癫痫药者。因此应避免联合使用,并积极监测患者药物浓度,实施个体化给药,促进安全合理使用。     

安神定志丸对癫痫小鼠的影响

目的:探讨安神定志丸对小鼠癫痫模型的影响。方法:通过给小鼠硝酸士的宁注射液、戊四氮及对小鼠进行电刺激制备癫痫发作模型,以生理盐水作对照,研究药物对动物癫痫发作的抑制作用。结果:安神定志丸对戊四氮所致的小鼠惊厥,能降低试验动物死亡率(P<0.05);对士的宁所致的试验动物惊厥,能延长惊厥发生的潜伏期(P<0.05)和死亡时间(P<0.05);能降低电惊厥动物的惊厥发生率(P<0.05)。结论:安神定志丸具有明显的抗癫痫作用。     

洋金花对电刺激大鼠皮层惊厥阈值及海马神经元形态结构的影响

目的观察洋金花对癫痫大鼠皮层惊厥阈值的影响及对癫痫大鼠海马神经元形态结构是否有保护作用。方法采用直接刺激大鼠皮层惊厥阈值测定模型作为观察对象,动态观察洋金花原生药、卡马西平对模型大鼠的惊厥阈值、海马神经元形态结构的影响。结果洋金花组在给药后大鼠惊厥阈值明显增高,与对照组比较,差异有统计学意义(P<0.05),但其抗惊厥作用较卡马西平为差。海马神经元形态结构变化以模型稳定组及模型对照组损害为重;洋金花组可见少数红色神经元及神经元消失,细胞间隙略增大;卡马西平组海马CA1区神经元在不同时段损害较洋金花组为重,但明显轻于模型对照组。结论洋金花可能通过其所含生物碱-东莨菪碱的M-胆碱能受体阻断作用发挥抗惊厥作用和神经元保护作用,其抗惊厥作用弱于卡马西平,但对惊厥神经元的保护作用强于卡马西平,这为中西医结合治疗癫痫,可能提供一个新的方法。     

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。     

卡马西平对青霉素点燃惊厥大鼠脑内GABA_A受体mRNA表达的作用

目的研究两种剂量卡马西平对青霉素慢性点燃大鼠的抗惊厥作用及对脑内GABAA受体mRNA表达的影响,从基因水平探讨卡马西平抗惊厥的作用机制。方法采用腹腔注射(ip)青霉素(3×106U.kg-1.d-1)慢性点燃大鼠惊厥模型,两种剂量卡马西平(50,100mg.kg-1×13d)ig给药,以痫性发作潜伏期和Racine惊厥行为分级标准为判定药效指标,观察卡马西平的抗惊厥作用。运用RT-PCR技术测定大鼠脑内GABAA受体mRNA表达量,分析卡马西平抗惊厥作用的新机制。结果两种剂量卡马西平ig给药后,均可使青霉素慢性点燃大鼠痫性发作的潜伏期延长,与模型对照组相比差异有统计学意义(P<0.01),同时使惊厥大鼠的发作程度均较模型对照组减轻。青霉素慢性点燃大鼠脑内GABAA受体mRNA表达减少,与正常对照组比较,差异有统计学意义(P<0.01);两种剂量卡马西平预防性干预组的GABAA受体mRNA表达量分别与模型对照组相比,差异均无显著性。结论两种剂量卡马西平对青霉素慢性点燃的惊厥发作均有明显的对抗作用,但抗惊厥机制与GABAA受体的基因表达无关。     

丙戊酸钠与苯妥英钠或卡马西平相互作用的血浓度观察

本文报告丙戊酸钠和苯妥英钠或卡马西平合用治疗各型癫痫９０例，丙戊酸钠使苯妥英钠和卡马西平血浓度下降；苯妥英钠和卡马西平是强有力的肝酶诱导剂，使丙戊酸钠血浓度降低，作者认为，抗癫痫药之间的相互作用错综复杂，临床上最好选择单一用药，昼避免联合用药。     

天竺桂挥发油镇痛、抗癫痫的作用

目的:研究天竺桂挥发油(CJO)的镇痛及抗癫痫作用。方法:天竺桂挥发油的镇痛药理实验采用扭体法、小鼠甩尾法等,抗癫痫作用采用最大电休克(MES)急性惊厥模型试验与戊四唑(PTZ)惊厥模型。结果:小剂量的天竺桂挥发油可显著减少醋酸致小鼠扭体次数及甩尾次数,镇痛效果明显;CJO50 mg.kg-1剂量组可明显降低MES惊厥率、显著延长PTZ潜伏期,但随剂量增加,抗癫痫作用减弱。结论:小剂量天竺桂挥发油具有明显的镇痛作用与良好的抗癫痫作用。     

卡马西平治疗癫痫的血药浓度及临床疗效分析

目的比较不同厂家卡马西平治疗癫痫的血药浓度及临床疗效。方法采用高效液相色谱法测定癫痫患者卡马西平血药浓度,将患者分组,分别给予得理多和国产卡马西平,比较两组血药浓度及疗效、不良反应、满意度等。结果得理多组达有效血药浓度比例较高,控制率及显效率较高(P<0.05),满意度较高于国产组(P<0.05),两组不良反应发生率无显著差异(P>0.05)。结论得理多疗效好于国产卡马西平。     

极缓慢加量减少卡马西平皮肤不良反应的回顾性研究

<正>卡马西平是临床一线抗癫痫药,近年来有关该药的不良反应报告较多。如何避免卡马西平使用过程中出现不良反应是临床医师经常要面对的问题。本研究调查了在我院使用卡马西平的部分患者,发现极缓慢加量可能有助于减少卡马西平皮肤不良反应,现汇报如下。1资料与方法1.1一般资料:本研究资料来自我院2006年1月至2012年12月的门诊癫痫患者。所有入选病例既往无卡马西平使用史,在我院首次使用,并建立     

托吡酯治疗癫痫的临床研究

目的：探讨低剂量托吡酯（商品名：妥秦,＜200mg)对癫痫发作的疗效。方法：33例癫痫患者采用妥泰单用或联合其他抗癫痫药治疗,起始剂量25mg.qd。另外40例患者采用卡马西平治疗作为对照。结果：妥秦治疗组的有效率（93．9％）明显高于卡马西平治疗组（77．5％）,P＜0．05,同时单一抗癫痫和联合抗癫痫疗效比较显效率有显著性差异（P＜0．05）,结论：妥泰对癫痫发作的疗效优于卡马西平,且妥秦单一用药优于联合用药。     

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。     

Imperatorin enhances the protective activity of conventional antiepileptic drugs against maximal electroshock-induced seizures in mice

The effects of imperatorin (8-isopentenyloxypsoralen; 9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one) on the anticonvulsant activity of four conventional antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) were studied in the mouse maximal electroshock seizure model. Results indicate that imperatorin (30 and 40 mg/kg, i.p.) significantly potentiated the anticonvulsant activity of carbamazepine against maximal electroshock-induced seizures by reducing its median effective dose (ED(50)) from 10.3 to 6.8 (by 34%; P<0.05) and 6.0 mg/kg (by 42%; P<0.01), respectively. Similarly, imperatorin (40 mg/kg, i.p.) markedly enhanced the antielectroshock action of phenobarbital and phenytoin, by lowering their ED(50) values from 19.6 to 12.2 mg/kg (by 38%; P<0.05-phenobarbital) and from 12.8 to 8.5 mg/kg (by 34%; P<0.05-phenytoin) in the maximal electroshock seizure test. In contrast, imperatorin (40 mg/kg, i.p.) did not affect the protective action of valproate against maximal electroshock-induced seizures in mice. Imperatorin at lower doses of 20 and 30 mg/kg had no significant effect on the anticonvulsant activities of conventional antiepileptic drugs in the mouse maximal electroshock seizure model. Pharmacokinetic evaluation of interaction between imperatorin (30 mg/kg, i.p.) and carbamazepine (6.8 mg/kg, i.p.) revealed a significant increase in total brain carbamazepine concentration after imperatorin administration, indicating a pharmacokinetic nature of interaction between these drugs. In cases of phenobarbital and phenytoin, imperatorin (40 mg/kg, i.p.) did not alter significantly total brain concentrations of phenytoin and phenobarbital in mice, and thus, the observed interactions in the maximal electroshock seizure test between imperatorin and phenobarbital or phenytoin were pharmacodynamic in nature. The present study demonstrates that imperatorin enhanced the antiseizure effects of carbamazepine, phenobarbital and phenytoin in the mouse maximal electroshock seizure model. However, the combination of imperatorin with carbamazepine, despite its beneficial effects in terms of seizure suppression in mice, was complicated by a pharmacokinetic increase in total brain carbamazepine concentration in experimental animals. In contrast, the combinations of imperatorin with phenytoin and phenobarbital, due to their beneficial antiseizure effects and no pharmacokinetic interactions between drugs in the brain compartment of experimental animals, deserve more attention and are of pivotal importance for epileptic patients as advantageous combinations from a clinical viewpoint.     

丁苯酞抗惊厥、抗癫痫作用探讨

目的观察丁苯酞对癫痫小鼠的影响。方法将小鼠84只分成6组,每组14只。溶媒对照组[PEG组,30%聚乙二醇400（PEG400）],模型组（30%PEG400＋致痫剂）,丁苯酞低剂量组（NL组,0.2g/kg）、中剂量组（NM组,0.4g/kg）、高剂量组（NH组,0.8g/kg）,阳性对照组,苯巴比妥钠组（PG组,20g/kg）,地西泮组（DG组,2.5g/kg）。小鼠腹腔注射丁苯酞后用士的宁及海人藻酸制作急性癫痫模型,以强直性惊厥发作潜伏期、癫痫持续状态发生的潜伏期等为判定药效指标,观察丁苯酞的抗惊厥、抗癫痫作用。结果在士的宁致癫痫模型中,NH组和PG组小鼠的病死时间延迟、强直性惊厥发作潜伏期延长、病死率及强直性惊厥的发生率降低,与MG组比较差异均有统计学意义（P〈0.05或P〈0.01）;与PG组比较,惊厥小鼠病死时间及病死率差异无统计学意义（P〉0.05）。与MG组比较,NH组海人藻酸引起的小鼠癫痫持续状态发作的潜伏期延长（P〈0.05）,但是小鼠癫痫持续状态的发生率未见明显减少;而DG组癫痫持续状态发作潜伏期明显延长,发生率大幅下降（P〈0.01）。结论丁苯酞具有较好的抗惊厥、抗癫痫作用。     

Determination of risk factors associated with seizure relapse after antiepileptic drug withdrawal

There is no consensus regarding the time of antiepileptic drug withdrawal and the relevant risk factors for seizure relapse. In this study, we aimed to determine the seizure relapse rates and the associated risk factors for seizure relapse in childhood epilepsy. Two-hundred sixty-six epileptic patients who discontinued the antiepileptic drug therapy after a seizure-free period of at least two years, were enrolled into the study. The data of the patients regarding sex, febrile convulsion history, family history, age at onset, type of epilepsy, total number of seizures and antiepileptic drugs, seizures during treatment, mental status, first and last electroencephalography, brain imaging findings, etiological factors and seizure relapse in the first two years after antiepileptic drug withdrawal were obtained from the patients’ files. Univariate logistic regression analysis was performed for each variable. The variables which were found to be statistically significant in univariate analysis, were included in multivariate logistic regression analysis. The overall seizure relapse rate after antiepileptic drug withdrawal was 19.2%. There were no significant differences for seizure relapse rate after antiepileptic drug withdrawal between patient groups with respect to sex, family history, type of epilepsy, febrile convulsion history, seizures before treatment, first electroencephalography findings, brain imaging findings and etiology. However, there were statistically significant differences for seizure relapse rate among patient groups concerning age at onset of epilepsy, new seizure during treatment, the total number of antiepileptic drugs, mental status, and last electroencephalography findings. We imply that the clinical status of the patients should be considered before the cessation of drug therapy rather than the etiological factors or laboratory findings.     

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。     

The interactions of atorvastatin and fluvastatin with carbamazepine, phenytoin and valproate in the mouse maximal electroshock seizure model

The aim of this study was to determine the influence of acute (single) and chronic (once daily for 7 consecutive days) treatments with atorvastatin and fluvastatin on the anticonvulsant potential of three antiepileptic drugs: carbamazepine, phenytoin and valproate in the mouse maximal electroshock-induced seizure model. Additionally, the effects of acute and chronic administration of both statins on the adverse effect potential of three antiepileptic drugs were assessed in the chimney test (motor performance) and passive avoidance task (long-term memory). To evaluate the pharmacokinetic characteristics of interaction between antiepileptic drugs and statins, the total brain concentrations of antiepileptic drugs were estimated with the fluorescence polarization immunoassay technique. Results indicate that atorvastatin at doses up to 80mg/kg in chronic experiment attenuated the anticonvulsant potential of carbamazepine by increasing its ED(50) value against maximal electroconvulsions. Acute fluvastatin (80mg/kg) enhanced the anticonvulsant potential of carbamazepine and valproate by decreasing their ED(50) values. Acute fluvastatin (80mg/kg) also markedly increased the total brain carbamazepine concentration by 61% in a pharmacokinetic reaction. Atorvastatin (acute and chronic) and fluvastatin (chronic) in combinations with valproate impaired long-term memory in mice. Both statins in combinations with all three antiepileptic drugs had no impact on their adverse effects in the chimney test. Based on this preclinical study, one can conclude that chronic administration of atorvastatin reduces the anticonvulsant action of carbamazepine and acute fluvastatin can enhance the anticonvulsant potency of the carbamazepine and valproate. The former interaction was pharmacokinetic in nature.     

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     

Influence of sexual hormone antagonists on the anticonvulsant action of conventional antiepileptic drugs against electrically- and pentylenetetrazol-induced seizures in mice.

The present results refer to the action of three gonadal steroid antihormones, tamoxifen (TXF, an estrogen antagonist), cyproterone acetate (CYP, an antiandrogen) and mifepristone (MIF, a progesterone antagonist) on seizure phenomena in mice. TXF and CYP at their lowest protective dose in the electroconvulsive threshold test, enhanced the antiseizure efficacy of some antiepileptic drugs. TXF (20 mg/kg) potentiated the protective activity of valproate, diphenylhydantoin and clonazepam, but not that of carbamazepine or phenobarbital, against maximal electroshock-induced convulsions in female mice. CYP (40 mg/kg) enhanced the anticonvulsant action of valproate, carbamazepine, diphenylhydantoin and clonazepam, but not that of phenobarbital, against maximal electroshock in male animals. MIF failed to affect the electroconvulsive threshold or the efficacy of antiepileptic drugs in maximal electroshock. The effect of TXF or CYP upon the electroconvulsive threshold and on the action of antiepileptics was not reversed by sex steroid hormones (estradiol, testosterone, progesterone). However, the TXF-induced elevation of the electroconvulsive threshold was abolished by bicuculline, N-methyl-D-aspartic acid and kainic acid, and partially reversed by aminophylline, strychnine being ineffective in this respect. The action of CYP on the threshold for electroconvulsions was partially reversed by bicuculline and aminophylline. Both glutamatergic agonists and strychnine remained ineffective in this respect. Moreover, the action of TXF or CYP on the activity of antiepileptics was not influenced by strychnine, and reversed to various extents by the remaining convulsants. In contrast to maximal electroshock, none of the three antihormones affected the protective action of antiepileptic drugs against pentylenetetrazol-induced seizures in mice. Neither TXF nor CYP altered the free plasma levels of antiepileptic drugs, so a pharmacokinetic interaction is not probable. The combined treatment of the two antihormones with antiepileptic drugs, providing 50% protection against maximal electroshock, did not affect motor performance in mice, and did not result in significant long-term memory deficits. Our data indicate that steroid receptor-mediated events may be indirectly associated with seizure phenomena in the central nervous system and can modulate the protective activity of some conventional antiepileptic drugs.     

Fluoxetine enhances the anticonvulsant effects of conventional antiepileptic drugs in maximal electroshock seizures in mice

The present study was designed to investigate the effects of fluoxetine (FXT), a selective serotonin reuptake inhibitor, on the effect of antiepileptic drugs (AEDs) in the maximal electroshock seizure (MES) model in mice. FXT at the doses of 25, 20 and 15 mg/kg significantly increased the electroconvulsive threshold. The antidepressant applied at the lower doses (10, 5 and 2.5 mg/kg) did not influence the threshold. Moreover, FXT (at the highest subprotective dose of 10 mg/kg) increased the anticonvulsive potential of carbamazepine (CBZ), diphenylhydantoin (DPH), valproate (VPA) and phenobarbital (PB), producing a dose-related decrease in their ED50 values against MES. Nevertheless, pharmacokinetic events may be involved in the interaction between FXT and PB or CBZ, since the antidepressant raised the total brain concentration of the two antiepileptics. FXT in combination with AEDs did not influence the motor performance in the chimney test and long-term memory. In conclusion, the data suggest that FXT modulates seizure processes in the brain and may be advantageous in the treatment of epilepsy in depressed patients, improving the seizure control in epilepsy.     

Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier through glutamate and cyclooxygenase-2 signaling

Increased expression of drug efflux transporters at the blood-brain barrier accompanies epileptic seizures and complicates therapy with antiepileptic drugs. This study is concerned with identifying mechanistic links that connect seizure activity to increased P-glycoprotein expression at the blood-brain barrier. In this regard, we tested the hypothesis that seizures increase brain extracellular glutamate, which signals through an N-methyl-d-aspartate (NMDA) receptor and cyclooxygenase-2 (COX-2) in brain capillaries to increase blood-brain barrier P-glycoprotein expression. Consistent with this hypothesis, exposing isolated rat or mouse brain capillaries to glutamate for 15 to 30 min increased P-glycoprotein expression and transport activity hours later. These increases were blocked by 5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate) (MK-801), an NMDA receptor antagonist, and by celecoxib, a selective COX-2 inhibitor; no such glutamate-induced increases were seen in brain capillaries from COX-2-null mice. In rats, intracerebral microinjection of glutamate caused locally increased P-glycoprotein expression in brain capillaries. Moreover, using a pilocarpine status epilepticus rat model, we observed seizure-induced increases in capillary P-glycoprotein expression that were attenuated by administration of indomethacin, a COX inhibitor. Our findings suggest that brain uptake of some antiepileptic drugs can be enhanced through COX-2 inhibition. Moreover, they provide insight into one mechanism that underlies drug resistance in epilepsy and possibly other central nervous system disorders.