Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs

4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([³H]Glu). 4-AP-induced [³H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca²⁺ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [³H]Glu release to 4-AP between 50–60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [³H]Glu release to 4-AP. We conclude that the decrease in [³H]Glu release linked to the direct blockade of presynaptic Na⁺ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [³H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K⁺ channels permeability.     

利培酮合并奥卡西平治疗精神分裂症兴奋躁动的比较研究

目的：评估奥卡西平辅助治疗兴奋躁动精神分裂症的疗效和安全性。方法：将符合中国精神障碍分类与诊断标准第3版中精神分裂症诊断标准并以兴奋躁动为主要表现的68例患者随机分为研究组（n=35）和对照组（n=33）,研究组应用抗精神病药物利培酮联合奥卡西平,对照组单一使用利培酮,观察6周。采用简明精神病量表（BPRS）和阳性与阴性症状量表（PANSS）兴奋因子、临床疗效总印象量表（CGI）、不良反应量表（TESS）在治疗前及治疗后第1、2、4周分别评估疗效和安全性。结果：研究组有效29例（82．9％）,对照组有效19例（57．6％）,两组有效率比较差异有统计学意义（X^2=5．229,P〈0．05）。研究组与对照组患者分别脱落1例和2例。研究组的主要不良反应为镇静（9例）、便秘（9例）、头晕（7例）、心动过速（6例）等,对照组的主要不良反应为便秘（11例）、口干（10例）、心动过速（7例）、锥体外系不良反应（6例）等。结论：奥卡西平能有效辅助治疗精神分裂症的兴奋状态。     

奥卡西平与碳酸锂治疗躁狂发作的疗效比较

［摘要］目的探讨奥卡西平与碳酸锂治疗躁狂发作的疗效与安全性。方法躁狂发作患者70例,随机分为奥卡西平组34例,碳酸锂组36例。奥卡西平组给予奥卡西平0.6～1.8 g•d 1,碳酸锂组给予碳酸锂0.5～1.5 g•d 1。两组均联合给予非典型抗精神病药物治疗,应用Beck Rafaelsen躁狂评定量表（BRMS）观察6周。结果两组治疗后BRMS评分均明显下降（均P＜0.01）。奥卡西平组治疗第1周末、第2周末的BRMS评分均显著低于碳酸锂组（均P＜0.05）,减分率显著高于碳酸锂组（P＜0.05）,临床有效率显著高于碳酸锂组（P＜0.05）。两组不良反应相似（P＞0.05）。结论奥卡西平联合非典型抗精神病药物控制躁狂发作的疗效优于碳酸锂,安全性良好。     

左乙拉西坦及奥卡西平对癫痫患儿丙戊酸钠及其代谢产物2-丙基-2-戊烯酸血药浓度的影响

目的:探讨左乙拉西坦(Levetiracetam,LEV)、奥卡西平(Oxcarbazepine,OXC)对丙戊酸钠(VPA)及其代谢产物2-丙基-2-戊烯酸(2-ene-VPA)血药浓度的影响。方法:共纳入114例在我院门诊就诊的癫痫病患儿,根据治疗方案分为VPA组(n=71),VPA+LEV组(n=23)以及VPA+OXC组(n=20)。采用RP-HPLC法测定VPA代谢产物2-ene-VPA的血药浓度,并采用SPSS 19.0软件进行统计学分析。结果:VPA+LEV组与VPA组相比,VPA血药浓度的差异无统计学意义(P=0.778);而VPA+OXC组中VPA的血药浓度较单独服用VPA组低,差异有统计学差异(P=0.004)。而在VPA组、VPA+LEV组、VPA+OXC组中,2-ene-VPA血药浓度的差异无统计学意义(P=0.082)。在VPA组中,VPA和2-ene-VPA血药浓度间的正相关关系具有统计学意义(R=0.278,P=0.019)。在VPA+LEV组及在VPA+OXC组中,VPA和2-ene-VPA血药浓度间的相关关系均没有统计学意义(P=0.138;P=0.334)。结论:VPA联合应用OXC时,需根据血药浓度监测结果调整VPA及OXC剂量,VPA联合应用LEV时无需调整VPA剂量;VPA与LEV或OXC合用时不会增加2-ene-VPA的中枢神经系统不良反应。     

Possible Interaction Between Oxcarbazepine and an Oral Contraceptive

The effect of oxcarbazepine (OCBZ) on the kinetics of an oral contraceptive containing ethinyloestradiol (EE) and levonorgestrel (LNG) was investigated in 13 healthy female volunteers who had previously received the contraceptive for at least 3 months. After 15 days of the first study cycle, each subject received, in addition to the oral contraceptive, 300 mg OCBZ on day 16, 300 mg twice daily on day 17, and 300 mg three times daily from day 18 of the first cycle to day 18 of the next menstrual cycle. The area under the curve values for both EE and LNG decreased when OCBZ was given with the oral contraceptive (p = 0.006, analysis of variance). The results indicate that OCBZ, like most antiepileptic drugs (AEDs), decreases the bioavailability of EE and LNG, perhaps by affecting metabolism or protein binding.     

Anticonvulsant Action of Oxcarbazepine, Hydroxycarbamazepine, and Carbamazepine Against Metrazol-Induced Motor Seizures in Developing Rats

Summary: Antimetrazol effects of carbamazepine (CBZ, 5, 12.5, 25, or 50 mg/kg), oxcarbazepine (OCBZ, 5, 10, 30, or 60 mg/kg), and hydroxycarbamazepine (HCBZ, the main human metabolite of OCBZ, 10, 30, or 60 mg/kg) were studied in 7–, 12–, 18–, 25–, and/or 90-day-old laboratory rats. No drug tested affected the incidence of minimal (clonic) metrazol seizures (mMs) in animals aged ≥18 days; in rats aged 7 or 12 days in which mMs are rare under control conditions, the incidence of mMs was increased by lower doses of CBZ and HCBZ. All drugs tested specifically abolished the tonic phase of major generalized tonic-clonic seizures (MMs) in a dose-dependent manner. In addition, CBZ and OCBZ were able to suppress all phases of MMs in the two youngest groups (7-and 12-day-old). There were no marked differences among the three drugs tested (CBZ, OCBZ, and HCBZ) on their action against metrazol-induced seizures during ontogenesis of rats; i.e., all these drugs appeared to possess an identical profile of anticonvulsant action.     

Cross-Reactive Skin Eruption with Both Carbamazepine and Oxcarbazepine

Summary: Oxcarbazepine (OCBZ), a 10-keto derivative of carbamazepine (CBZ) has been reported to have a similar range of efficacy and fewer unwanted effects than CBZ since it is a prodrug for the monohydroxy derivative (MHD). A cross-reactivity of only 1 in 4 has been reported between OCBZ and CBZ. For these reasons, we tried OCBZ with 3 consecutive patients with poorly controlled epilepsy who had had a therapeutic response to CBZ but in whom CBZ was discontinued because of serious skin reaction. Each patient had a similar skin response after exposure to only 600–900 mg OCBZ, which suggests a need to practice caution when substituting OCBZ for CBZ in patients known to have serious skin reaction to CBZ.     

奥卡西平对癫痫患儿骨代谢的影响

目的 探讨长期口服奥卡西平(OXC)抗癫痫治疗对癫痫患儿骨代谢的影响,为临床用药提供指导。 方法 设健康对照组41例,选择单独服用OXC的41例癫痫患儿作为病例组,记录服用OXC6个月前后癫痫患儿及同期对照组骨代谢生化指标：如血钙(Ca₂ )、血磷 (P₃ )、1,25-(OH)₂Vit D₃、 甲状旁腺素 (PTH)、骨特异性碱性磷酸酶 (BALP)、骨钙素 (BGP)、降钙素 (CT) 和尿脱氧吡啶啉 (DPD),尿肌酐(Cre)。结果 单独应用OXC抗癫痫治疗6个月后,病例组1,25-(OH)₂VitD₃水平(23.53±3.67)低于健康对照组(26.11±3.92),差异有统计学意义 ( t=3.08,P < 0.05);病例组血清BALP水平(18.74±4.02)低于健康对照组(22.97±6.31),差异有统计学意义(t = 3.62, P < 0.05);病例组血清BGP水平(5.81±1.02)低于健康对照组(6.51±1.98),差异有统计学意义 (t=2.01,P < 0.05),病例组尿液中DPD/ Cre水平(25.33±8.33)高于健康对照组(21.01±9.52),差异有统计学意义(t=2.19, P < 0.05);两组间血钙(Ca₂ )、血磷 (P₃ )、甲状旁腺素 (PTH)、降钙素 (CT) 水平差异无统计学意义。结论 长期服用奥卡西平可致骨代谢异常,增加了骨吸收降低了骨形成,临床使用时应注意其不良反应。     

UPLC法测定拉莫三嗪和奥卡西平活性代谢物血清药物浓度

目的建立超高效液相色谱(UPLC)同时测定人血清中拉莫三嗪(Lamotrigine,LTG)和奥卡西平活性代谢物10-羟基卡马西平(Monohydroxy-carbazepine,MHD)浓度的方法。方法色谱柱为Waters ACQUITY UPLCTM BEH C_(18)柱(2.1 mm×50 mm,1.7μm),柱温30℃,流动相:乙腈-10 mmol/L乙酸铵(20∶80;甲酸调pH=4),流速:0.2 mL/min,进样量2μL,检测波长240 nm。结果血清中内源性物质对样本测定无干扰,LTG和M HD分别在1~40μg/mL和1.25~80μg/mL浓度范围内线性关系良好,相关系数r分别是0.999 8和0.999 7。本方法两个化合物准确度RE值在±10%范围内,批内和批间精密度RSD值均<10%,LTG回收率73%~80%,M HD回收率89%~97%。结论本法操作简便、专属性强、灵敏度高、重现性好,符合生物样品的分析要求,适用于LTG和奥卡西平活性代谢物MHD的浓度监测。     

奥卡西平诱导癫痫患者低钠血症危险因素分析及血清钠水平监测建议

摘 要 目的:探讨奥卡西平（OXC）诱导癫痫患者低钠血症的发生率及危险因素,对服用OXC癫痫患者血清钠水平监测提出建议,为临床合理用药提供参考。方法：158例服用OXC的癫痫患者,根据血钠水平检测结果分为正常血钠组和低钠血症组,比较两组临床资料,多因素Logistic回归分析OXC诱发低钠血症的危险因素。结果：OXC诱导低钠血症的发生率为16.5%,多因素分析结果表明OXC剂量（P<0.01）、合用利尿药（P<0.01）、合用钙离子拮抗药（P<0.05）是OXC诱发低钠血症可能的独立危险因素。结论：大部分服用OXC的癫痫患者不必常规监测血钠。但对本身患有可能诱发低钠血症的疾病、高龄、服药剂量大、同时服用能降低血钠水平的药物等低钠血症发生风险高的患者,定期监测血钠非常必要。