唑尼沙胺对癫痫大鼠血清及脑组织 NO 含量及 NOS 活性的影响

摘要： 目的 探讨新型抗癫痫药物唑尼沙胺对癫痫大鼠血清及脑组织 NO 含量及一氧化氮合酶 （NOS） 活性的影响。方法 50 只健康雄性 SD 大鼠中随机抽取 8 只为正常对照组, 剩余 42 只全部腹腔注射戊四氮制成癫痫模型, 从中随机抽取 24 只, 以完全随机分组法分为癫痫模型组、 唑尼沙胺组及苯巴比妥组, 监测各组大鼠经药物干预后血清及脑组织 NO、 丙二醛（MDA）含量及 NOS、 超氧化物歧化酶（SOD）的活性变化。结果 35 只（83%）大鼠模型制备成功; 戊四氮致痫大鼠的脑电图中均可见阵发性癫痫波; 与正常对照组比较, 癫痫模型组和唑尼沙胺组大鼠的血清和脑组织的 NO、 MDA 含量及 NOS 活性明显升高, SOD 活性下降; 苯巴比妥组脑组织 NO、 MDA 含量升高, SOD 活性下降, 血清 MDA 含量升高。与癫痫模型组比较, 唑尼沙胺组和苯巴比妥组大鼠血清和脑组织 NO、 MDA 含量及 NOS 活性明显降低, SOD 活性升高, 差异有统计学意义 （P＜0.05）。结论 唑尼沙胺通过降低脑组织 NO 含量而发挥其抗癫痫作用。     

唑尼沙胺作为添加用药治疗部分性癫痫发作的有效性和安全性

唑尼沙胺(zonisamide)是一种通过多种机制产生作用的新型抗癫痫药物(AEDs),自1989日本上市,美国于2000年批准上市,欧洲是2005年被批准上市。唑尼沙胺是一种广谱抗癫痫药,临床研究表明,唑尼沙胺是对多种类型的癫痫有效,包括对癫痫部分性发作或继发性全身发作、全身性强直阵挛发作均有效。本文将阐叙唑尼沙胺作为添加用药治疗部分性癫痫的有效性和安全性。     

唑尼沙胺治疗儿童耐药性癫痫的研究进展

目的:为唑尼沙胺治疗儿童耐药性癫痫的临床实践提供参考。方法:查阅近年来国内外相关文献,对唑尼沙胺治疗儿童耐药性癫痫的研究进展进行归纳和总结。结果:唑尼沙胺是一种广谱的新型抗癫痫药,具有较好的生物利用度,口服吸收迅速完全。儿童用药的剂量范围为2~12 mg/(kg·d),维持剂量为8~8.5 mg/(kg·d)。唑尼沙胺治疗儿童耐药性癫痫安全有效,可作为儿童癫痫综合征(婴儿痉挛症、Lennox-Gastaut综合征和青少年肌阵挛性癫痫)的二线药物。结论:唑尼沙胺单药或添加治疗儿童耐药性癫痫具有良好的疗效、安全性及耐受性,为儿童耐药性癫痫治疗提供更多选择。     

抗癫痫药物唑尼沙胺易致代谢性酸中毒

美国FDA近日要求抗癫痫药物唑尼沙胺（zonisamide）的生产厂商在其产品标签上增加有关该药存在代谢性酸中毒风险的警告。唑尼沙胺的产品标签中此前已列出严重皮肤反应、Stevens—Johnson综合征以及有关抑郁和自杀倾向的认知／神经精神病方面的不良反应。     

唑尼沙胺添加治疗耐药性癫痫部分性发作的临床疗效和安全性评价

目的 观察在耐药性癫痫部分性发作治疗中,唑尼沙胺作为添加治疗的临床疗效和安全性,探讨唑尼沙胺在耐药性癫痫中的治疗作用.方法 采用随机双盲、安慰剂对照、前瞻性研究方法.耐药性部分性癫痫45例,随机进入试验组与对照组,分别服用唑尼沙胺或安慰剂,观察病人的发作情况及不良反应.结果 试验组有效率17%(4例),显效率17%(4例),完全控制率17%(4例);对照组有效率14%(3例),显效率9%(2例),完全控制率0%(0例);2组比较有显著差异(P＜0.05).试验组不良反应率(75%)高于对照组(50%),但2组比较无显著差异(P＞0.05).结论 唑尼沙胺作为耐药性癫痫的添加治疗,疗效好,且不良反应轻而少.     

新型抗癫痫药唑尼沙胺临床应用

报道唑尼沙胺（唑利磺胺）临床应用，耐受性，药物相互作用，及用法与用量。     

毛细管色谱法测定唑尼沙胺中的有机溶剂残留量

目的建立毛细管气相色谱法测定唑尼沙胺中的有机溶剂残留量。方法用DB-624毛细管气相色谱柱,FID检测器,以正丙醇为内标进行测定。结果甲醇、乙醇、乙酸乙酯、乙酸的线性范围分别为15.029~240.464 mg.L-1(r=0.999 9)、24.964~399.424 mg.L-1(r=1)、25.02~400.32 mg.L-1(r=0.999 9)、24.99~399.84 mg.L-1(r=0.999 9);甲醇、乙醇、乙酸乙酯、乙酸的平均回收率分别为99.5%、99.0%、98.9%、99.2%;RSD分别为1.2%、1.4%、1.2%、1.5%1(n=9)。结论方法简单、灵敏、准确、重现性好,适用于唑尼沙胺中的有机溶剂残留量的测定。     

An assessment of zonisamide as an anti-epileptic drug

A brief review of epilepsy as a disease, anti-epileptic drugs and methods of evaluation of anti-epileptic drugs are presented as a background for assessment of zonisamide, which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. Chemically, zonisamide is classified as a sulphonamide and is unrelated to other anti-epileptic drugs. The mode of action of zonisamide remains unclear, but likely mechanisms are blockade of sodium and T-type calcium channels. It is also shown to have some neuroprotective effect against hypoxia and ischaemia. It has a liner pharmacokinetics with excellent oral bioavailability. Zonisamide has been approved for use in Japan for ten years prior to approval in USA and Europe. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures) and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures. The efficacy and safety was confirmed in trials conducted in USA and Europe in adults as well as children. Zonisamide compares favourably with other newly introduced drugs and has the potential for development as a monotherapy for epilepsy.     

MC-002对脑缺血再灌注损伤大鼠脑组织及血清中NO及NOS的影响

目的 研究MC-002对脑缺血再灌注损伤大鼠脑组织及血清中一氧化氮（NO）、一氧化氮合酶（NOS）含量的影响,探讨其对脑缺血再灌注损伤保护作用的机制.方法 采用改良线栓法,建立大鼠大脑中动脉栓塞（MCAO）脑缺血再灌注模型.将雄性SD大鼠随机分为假手术组、模型组、奥扎格雷钠组（18mg/kg）和MC-002高、中、低剂量组（30、18、10.8mg/kg）.缺血再灌注24h后检测脑组织及血清中NO含量、NOS活性.结果 与假手术组相比,模型组脑组织和血清中NO含量和NOS活性明显升高;与模型组相比,MC-002高、中、低剂量组脑组织和血清中NO含量和NOS活性均明显降低（P＜0.01、0.05）.结论 MC-002对大鼠脑缺血再灌注损伤具有明显的保护作用,其机制可能与降低NOS活性,减少NO含量有关.     

Zonisamide in the treatment of epilepsy

Introduction: Epilepsy affects approximately 3 million people in the USA and up to 2% of the worldwide population. The yearly direct medical cost of epilepsy in the USA alone is estimated to be $9.5 billion. Epilepsy affects both children and adults and can significantly impair quality of life. Zonisamide is a second-generation antiepileptic drug (AED) that has broad-spectrum efficacy, a favorable side-effect profile and simpler dosing than earlier drugs.

Areas covered: The history of the development of zonisamide is reviewed in this paper. The data available demonstrating zonisamide's mechanism of action as a voltage-gated sodium channel inhibitor, a T-type calcium channel inhibitor, an enhancer of GABA release and an inhibitor of glutamate release are also reviewed. Four key Phase III clinical trials are reviewed in detail, as are subsequent postmarketing trials that have expanded the therapeutic indication for zonisamide.

Expert opinion: From the available clinical data, zonisamide is a viable first-line and adjunctive therapeutic for partial-onset epilepsy and should be considered as an adjunctive therapeutic for a wide-range of generalized epilepsies.     

帕金森病合并癫痫的治疗

帕金森病和癫痫均为常见的神经系统慢性疾病,但帕金森病合并癫痫在临床上较为少见,部分研究显示帕金森病患者癫痫发作风险增加。脑深部电极刺激术为帕金森病外科治疗的主要选择,但其并发症包括癫痫发作,与较高的发病率和死亡率有关。此外,帕金森合并癫痫患者认知障碍风险增加,一线治疗药物胆碱酯酶抑制剂存在着诱发或加重癫痫发作的可能,而唑尼沙胺是目前唯一可用于帕金森病治疗的抗癫痫药物。本文就帕金森病合并癫痫患者治疗过程中的关键问题进行阐述,以期为临床治疗提供参考。     

血必净对急性胰腺炎大鼠血清一氧化氮的影响

目的探讨急性胰腺炎(Acute pancreatitis,AP)大鼠血清一氧化氮(Nitric oxide,NO)的变化及血必净注射液对其的影响。方法将90只SD大鼠随机分为假手术组、急性胰腺炎组、血必净组,各组再分为3、6、12 h亚组,假手术组开腹后仅行简单的胰腺翻动,急性胰腺炎组开腹后经十二指肠乳头逆行胆胰管注射5%牛黄胆酸钠建立AP模型,血必净组在AP组基础上予血必净注射液治疗,分别在各时间点采血观察血清中淀粉酶(AMY)、一氧化氮(NO)的变化,并进行胰腺组织病理学检查。结果与假手术组相比,AP组中AMY、NO浓度明显增高,差异有统计学意义(P<0.05);与AP组相比,血必净组中AMY、NO浓度明显降低,差异有统计学意义(P<0.05),光镜下AP组胰腺组织损伤明显,而血必净组损伤明显改善。结论 NO参与急性胰腺炎的发生发展过程,血必净注射液能显著降低血清NO,减轻胰腺组织的损伤。     

癫痫患者脑部病变的CT诊断

目的探讨症状性癫痫的CT定位、定性诊断。方法搜集110例的癫痫患者进行回顾性分析。CT扫描采用常规平扫,部分患者局部薄层扫描,59例强化扫描。结果先天发育异常者71例,有单一异常,亦有多种异常并存者;其中脑裂畸形31例、灰质异位13例、胼胝体发育不良21例、透明隔发育异常23例、脑回畸形4例。血管性病变者18例,其中动静脉畸形13例、海绵状血管瘤2例、SWS3例。肿瘤性病变者9例,其中星形细胞瘤7例、少突胶质细胞瘤2例。软化灶者12例,其中产伤5例、外伤7例。结论CT扫描对各种脑致癫痫病变的定位定性具有很大价值。     

颞叶癫痫儿童脑海马组织内 BDNF表达变化的意义

目的：探讨脑源性神经营养因子（brain derived neurotrophic factor,BDNF）在颞叶癫痫（temporal lobe epilepsy, TLE）发病机制中的作用。方法观察组为2012年3月-2013年3月在某医院神经外科癫痫中心16例TLE患儿术中切除的海马脑组织,对照组为2011年9月-2013年3月某医院神经外科8例非癫痫手术患儿的海马脑组织。标本采用免疫组化SABC法进行检测。免疫组化结果的判定以显微镜下观察,按每张切片的阳性细胞着色程度及数量,采用积分综合计量,并采用Ridit分析。结果按照显微镜下观察评分对两组数据进行分类,经Ridit 分析可知两组分级差异有统计学意义（ Hc＝9.2472,P＜0.01）,故认为观察组海马脑组织中BDNF表达强于对照组中海马脑组织BDNF表达。结论 BDNF在颞叶癫痫患儿的海马脑组织中表达增强,可能在颞叶癫痫的发病机制中起重要作用。     

Zonisamide in the treatment of epilepsy

Importance of the field: More than 1 million epilepsy patients suffer from insufficiently controlled epilepsy, both in the USA and in Europe. Zonisamide is an antiepileptic drug with multiple mechanisms of action, corresponding to efficacy in diverse epilepsy syndromes.

Areas covered in this review: Here, an update on pharmacodynamics, pharmacokinetics, clinical efficacy and safety in childhood and adult epilepsies is given based on an analysis of controlled and uncontrolled studies, European, US and East Asian, and on clinical experience with zonisamide (ZNS) published up to 2009.

What the reader will gain: Evidence is presented that ZNS is effective not only in adult focal epilepsies, for which it has been approved in the USA and in Europe, but also may offer treatment options for compassionate use in a spectrum of difficult-to-treat epilepsy syndromes. Its favorable pharmacokinetic profile allows for easy combination with most available antiepileptic drugs.

Take home message: Provided that additional studies on ZNS are performed to extend approval and to generate comparative data, ZNS has a potential to gain importance in the treatmnt of a wide spectrum of epilepsy patients.