Lamotrigine-antiparkinsonian activity by blockade of glutamate release?

Summary Recent experiments provide evidence that the NMDA-antagonist MK-801 has a locomotor-stimulating effect in monoamine-depleted rodents. These findings are based upon a hypothetical pathway-circuit including the basal ganglia as a model reflecting hypo- and hyperkinetic movement disorders. We have treated 5 patients suffering from Parkinson's disease with the antiepileptic drug lamotrigine which does not appear to be an NMDA-antagonist but acts functionally as a glutamate antagonist by inhibition of presynaptic glutamate release.     

氟桂利嗪和拉莫三嗪对胎鼠缺血缺氧性脑损害的保护作用

目的研究氟桂利嗪(FNZ)、拉莫三嗪(LTG)及两药联合经孕鼠给药,对胎鼠宫内缺血缺氧性脑损害的保护作用。方法将孕20 d Wistar大鼠40只,随机均分为FNZ组、LTG组、FNZ LTG组和对照组。前3组大鼠于脑缺血缺氧术前3 d开始灌胃给药,每天1次,分别为FNZ 0.5 mg/(kg.d),LTG 10 mg/(kg.d),FNZ 0.5 mg/(kg.d) LTG 10 mg/(kg.d)。第3天给药后3 h,每组取8只孕鼠制作宫内缺血缺氧模型,剩余2只孕鼠直接行剖宫产取胎鼠,每胎5只。于缺血缺氧后6、12、24、48 h分别取胎鼠血清0.5 ml,采用ELISA法测定血清神经元特异性烯醇化酶(NSE)和酸性钙结合蛋白(S-100)水平。结果胎鼠缺血缺氧后,血清NSE和S-100水平明显升高。FNZ组、LTG组及FNZ LTG组胎鼠缺血缺氧后各个时间点血清NSE和S-100较对照组明显降低,差异均有极显著性意义(均P<0.01)。联合用药组效果更明显,组间比较差异亦有极显著性意义(P<0.01)。结论产前预防性灌胃FNZ、LTG对胎鼠宫内缺血缺氧性脑损伤具有保护作用,联合用药效果更明显。     

Treatment-refractory bipolar disorder: classification to aid in clinical management

Bipolar disorder is an illness with complex symptomatology that encompasses severe symptoms of mood and thought disorder and can limit the cognitive range of human brain functioning. The Diagnostic and Statistical Manual, 4th edition and International Classification of Mental Disorder recommend subgroups of bipolar disorder based on symptoms, illness severity, and frequency of episodes. Pharmacological agents commonly used in the management of bipolar disorder include lithium; anticonvulsants, such as valproate, carbamazepine and lamotrigine; and recent years have witnessed increasing use of atypical antipsychotics. There are several intra- and inter-class differences in these compounds, especially relating to polarity of mood episode under consideration. Monotherapy trials have focused on efficacy of the compounds; few have explored combination therapy, especially in patients failing to respond or inadequately responding to one agent. Clinicians have frequently prescribed two or more compounds to stabilize moods. Monotherapy treatment of bipolar manic episode with various compounds including atypical antipsychotics, mood stabilizers such as lithium, valproic acid and carbamazepine yielded response rates of 50%. However, combination therapy of atypical antipsychotics with valproic acid or lithium offered an additional 20% improvement in the response rates. The article will review published data on augmentation studies, comment on case reports published in treatment-refractory bipolar disorder, and propose a new classification guideline for staging treatment-refractory bipolar disorder.     

癫痫患者丙戊酸与拉莫三嗪药代动力学相互作用研究

目的 考察癫痫患者合用丙戊酸(VPA)与拉莫三嗪(LTG)的药代动力学相互作用.方法 将纳入的癫痫患者随机分为3组:VPA组276例、LTG组254例和合用组334例.VPA组患者每天口服VPA 500～1000 mg,LTG组每天口服LTG 100～200 mg,合用组用VPA+LTG.高效液相色谱-质谱联用法测定V...     

高效液相色谱法测定人血浆中拉莫三嗪的浓度

目的建立测定人血浆中拉莫三嗪浓度的高效液相色谱法。方法色谱柱为SunFire C18(4.6 mm×250mm,5μm),流动相为水-乙腈-三乙胺(64.5:35:0.5,v/v/v),磷酸调节pH至6.5,流速为1.0 mL·min-1,血浆标本经乙酸乙酯-二氯甲烷(75:25,v/v)提取后,在237 nm波长下进行检测。结果拉莫三嗪在0.312 5⁴0.0μg·mL-1与峰面积呈良好的线性关系(Y=0.047 2X+0.069 3,r2=0.999 2),相对回收率均在82%40.0μg·mL-1与峰面积呈良好的线性关系(Y=0.047 2X+0.069 3,r2=0.999 2),相对回收率均在82%¹05%,日内和日间RSD均<5%。结论该方法专属性强、准确度好、灵敏度高、操作简便,适合临床上对拉莫三嗪血药浓度的常规监测。     

Conversion from immediate-release to extended-release lamotrigine improves seizure control

BackgroundImmediate release lamotrigine (LTG-IR) dosing can be limited by peak toxicity. It is thought that peak levels are responsible for some adverse effects such as dizziness, blurred vision, double vision and unsteadiness. At the same time, trough levels may be associated with reduced seizure threshold. The use of extended release lamotrigine (LTG-XR) to replace LTG-IR will be associated with less fluctuation in drug levels-lower peak levels may reduce adverse effects and higher trough levels may improve seizure control. This hypothesis was tested by analyzing seizure control and adverse effects before and after conversion from LTG-IR to LTG-XR in patients who underwent such conversion in 2009–2011.MethodsWe searched our patient database to identify patients converted from LTG-IR to LTG-XR for persistent seizures or adverse effects from August 2009 until December 31, 2011. We included only patients who took LTG-IR and LTG-XR for at least 6 months each. We excluded patients with nonepileptic seizures, progressive cause of epilepsy, or not keeping a seizure record. We collected the following parameters: age at conversion, LTG-IR dose and dosing schedule, duration on that dose, LTG-XR dose and dosing schedule, LTG serum level before and after conversion, duration of LTG-XR treatment, seizure frequency before and after conversion, and change in adverse experience profile. We also recorded baseline AEDs and any AED change during the course of the analysis.ResultsFifty five patients (26 female) satisfied the inclusion/exclusion criteria. Their mean age was 45 years (range 23 to 86). Ten were on LTG-IR monotherapy, 24 took LTG-IR plus one other AED, most commonly levetiracetam, and the remaining 21 took LTG-IR plus at least 2 other AEDs. The mean LTG-IR dose was 544 mg/day (range 150–1100 mg/day). The mean LTG-IR serum level was 11.6 (available in 53 patients-range 4.6–21 mcg/ml). Twenty six patients were converted to the same dose and one patient took a mixture of LTG-XR and LTG-IR at the same total daily dose, while 21 had their dose slightly increased and 7 had their dose slightly decreased due to adverse effects. The mean serum level after conversion was 11.8 (available in 49 patients-range 2.6–21.2 mcg/ml). As a result of the conversion, 26 patients (47%) experienced >50% reduction in seizure frequency. There was a 46% median reduction in seizure frequency overall. Seven patients reported improvement in adverse effects.ConclusionA conversion from LTG-IR to LTG-XR can help improve seizure control in some individuals with drug-resistant epilepsy, in addition to improving tolerability. While it is indicated in individuals experiencing peak adverse effects, it should also be considered in patients who have received incomplete seizure control from LTG-IR.     

Review of lamotrigine and its clinical applications in epilepsy

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.     

不同剂量拉莫三嗪治疗老年癫痫的比较研究

目的 探讨不同剂量拉莫三嗪治疗老年癫痫患者的临床疗效。方法 选择2014年7月—2018年2月洛阳市第三人民医院神经内科诊治的老年癫痫患者88例作为研究对象,根据拉莫三嗪使用剂量分为对照组（40例）和观察组（48例）。对照组患者给予大剂量拉莫三嗪片治疗,拉莫三嗪起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量100 mg/d,维持100 mg/d治疗观察至第8周。观察组患者给予小剂量拉莫三嗪片治疗,起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量50 mg/d,维持50 mg/d治疗观察至第8周。观察两组患者的临床疗效,同时比较两组患者蒙特利尔认知评估量表（MoCA）评分、P300潜伏期、波幅和不良反应情况。结果 治疗后,对照组和观察组总有效率分别为97.5%、97.9%,两组对比差异无统计学意义。治疗后,两组患者的MoCA评分均显著高于治疗前,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后的MoCA评分显著高于对照组,两组比较差异具有统计学意义（P<0.05）。治疗后,观察组的P300潜伏期显著降低,波幅明显升高,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后P300潜伏期及波幅显著优于对照组,两组比较差异具有统计学意义（P<0.05）。观察组治疗期间的不良反应发生率为6.3%,显著低于对照组的32.5%,两组比较差异具有统计学意义（P<0.05）。结论 相对于大剂量,小剂量拉莫三嗪治疗老年癫痫患者能达到很好的疗效,能减少不良反应的发生,改善患者的神经电生理功能与认知功能。