托吡酯与卡马西平治疗部分性癫痫发作的临床疗效评价

目的 观察托吡酯与卡马西平对部分性癫痫发作的临床疗效及用药安全性.方法 将我院2012年8月至2013年10月收治的85例部分性癫痫发作患者按照就诊顺序分为两组,对照组40例采用卡马西平治疗,观察组45例给予托吡酯治疗,比较两组临床疗效及不良反应发生情况.结果 观察组总有效率为93.33％,显著高于对照组的75.00％（x2=7.229,P＜0.05）;观察组不良反应发生率为28.89％,显著低于对照组的47.50％ （x2=6.308,P＜0.05）.结论 托吡酯治疗部分性癫痫发作效果优于卡马西平,且不良反应少,具有较好的临床应用价值.     

Carbamazepine treatment of generalized tonic–clonic seizures in idiopathic generalized epilepsy

PurposeEvaluate the efficacy of carbamazepine in the treatment of idiopathic generalized epilepsy (IGE).MethodThe response of five patients with IGE, who experienced primarily generalized tonic–clonic seizures which were refractory to multiple antiepileptic drugs, is reported.ResultsCarbamazepine controlled multiple seizure types and did not induce or increase the frequency of myoclonic or absence seizures in these patients. Many family members also responded favorably to carbamazepine.ConclusionCarbamazepine can be used with caution as an alternative treatment option for refractory IGE, especially in cases in which the main seizure type is generalized tonic–clonic.     

Cardiac function and antiepileptic drug treatment in the elderly: A comparison between lamotrigine and sustained-release carbamazepine

Purpose: To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy. Methods: The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double‐blind 40‐week trial, which compared the efficacy and tolerability of LTG and sustained‐release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12‐lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40‐week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR‐corrected QT) intervals were assessed and compared between groups. Results: Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline. Discussion: Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects.     

Mutated Nicotinic Receptors Responsible for Autosomal Dominant Nocturnal Frontal Lobe Epilepsy are More Sensitive to Carbamazepine

PURPOSE: The recent linkage between a genetically transmissible form of epilepsy (ADNFLE) and mutations within the alpha4 subunit, one component of the major brain neuronal nicotinic acetylcholine receptor (nAChR), raises the question of the role of this receptor in epileptogenesis. Although acting by different mechanisms, the two genetic alterations so far identified both render the nAChR less efficient. In view of the high sensitivity of ADNFLE to carbamazepine (CBZ), we studied the effects of this drug and of valproate (VPA) on the human alpha4beta2 nAChR and its mutations. METHODS: The alpha4beta2 nAChRs from control and mutant alpha4 subunits were reconstituted in Xenopus oocytes and investigated by using a dual-electrode voltage clamp technique. Acetylcholine (ACh)-evoked currents recorded in the absence or presence of antiepileptic drugs (AEDs) were studied to analyze the mode of action of these compounds. RESULTS: ACh-evoked currents at the human alpha4beta2 nAChR were readily and reversibly inhibited by approximately 100 microM CBZ. This compound was found to be a noncompetitive inhibitor of the nAChR, which probably acts by entering the channel and causing a blockade by steric hindrance. Dose-response inhibition curves determined on the control receptor and on ADNFLE-mutant receptors showed a greater sensitivity of the mutants to CBZ, with median inhibitory concentrations (IC50s) in the range of the antiepileptic plasma levels of CBZ. In contrast, VPA had nearly no effect on control and mutant nAChRs. CONCLUSIONS: CBZ inhibits the neuronal alpha4beta2 nAChRs at pharmacologic concentrations, with ADNFLE mutants displaying about threefold higher sensitivity to this compound. The increased sensitivity of these mutant receptors supports the hypothesis that the antiepileptic activity of CBZ can, at least to some extent, be attributed to the nAChR inhibition.     

Adjustment of Carbamazepine Dose to Offset the Effects of the Interaction with Remacemide Hydrochloride in a Double-Blind, Multicentre, Add-On Drug Trial (CR2237) in Refractory Epilepsy

Summary: Purpose: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double-blind, add-on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer.
Methods: Patients taking CBZ entered a 4-week run-in period to stabilise their dosage regimen to Tegretol tablets and blinded capsules containing Tegretol tablets. They then entered an 8-week baseline period during which variation of plasma CBZ concentration was used to derive an individual Shewart Control Chart for each patient. These charts were used to define the threshold for CBZ dose reduction after the addition of trial drug. Where necessary the unblinded observer adjusted that portion of the daily dose of CBZ concealed in the opaque capsules, thereby maintaining the blind for the investigator and the patient.
Results: CBZ dosage reductions ranging from 14 to 50% were required by 63% of patients who received REM. Substantial increases in plasma CBZ concentration, which would have confounded the results of the trial, were thus avoided. The small increases in CBZ concentration that occurred in spite of this procedure were of similar magnitude in responders (patients who experienced ≤50% reduction in seizure frequency during treatment) and nonresponders, and in both groups the mean increase was <1 mg/L.
Conclusions: The method is offered as a model solution for problems caused by pharmacokinetic interactions in add-on trials.     

妥泰治疗原发性三叉神经痛的疗效观察

目的　探讨妥泰治疗原发性三叉神经痛的疗效及安全性。方法　单用妥泰治疗 ,全部病例由专人治疗观察 ,观察其临床疗效、剂量及副作用。结果　妥泰治疗原发性三叉神经痛总有效率为 88% ,剂量为 5 0～ 40 0mg·d-1,未见明显的毒副反应。结论　妥泰治疗原发性三叉神经痛安全有效     

Discontinuation of Phenytoin and Carbamazepine in Patients Receiving Felbamate

Five patients participated in a controlled discontinuation of phenytoin (PHT) and carbamazepine (CBZ) after a study in which all subjects had felbamate (FBM) added to both PHT and CBZ. Four subjects (three women and 1 man aged 23-36 years) completed the protocol. Mean total seizure frequency per day with PHT and CBZ was 1.33 +/- 0.93 (mean +/- SEM), decreasing to 0.87 +/- 0.71 with addition of FBM, and 0.82 +/- 0.78 after discontinuation of PHT. Only one subject tolerated discontinuation of CBZ; the other three had dosage reductions of 33, 54, and 63%. Toxicity attributable to FBM was not observed, and patients often described less severe seizures. Results from four refractory patients indicated that FBM was able to replace PHT and reduce the need for CBZ. In addition, as PHT dosages were reduced, FBM clearance decreased 21%. As the CBZ dosages were reduced. FBM clearance decreased an additional 16.5%.     

卡马西平联合甲钴胺治疗原发性三叉神经痛46例对照研究

目的观察和评价卡马西平联合甲钴胺与卡马西平单独治疗原发性三叉神经痛的临床效果。方法采用随机、对照、开放性临床试验,入选46例原发性三叉神经痛患者,随机分为甲钴胺 卡马西平组和卡马西平组。采用视觉模拟评分法(VAS)对疼痛进行评估并比较治疗前后的效果。结果联合用药组较单药治疗组起效快,卡马西平用量少,不良反应发生率低。结论联合用药治疗原发性三叉神经痛是一种非常有效和安全的方法,值得进一步研究。     

Dihydropyridine Calcium Antagonists in Mice: Blood and Brain Pharmacokinetics and Efficacy Against Pentylenetetrazol Seizures

Dihydropyridine calcium antagonists are candidate anticonvulsants, but little is known of their penetration into brain. Nifedipine (NFD) and nimodipine (NMD) pharmacokinetics were compared in mouse blood and brain, and their activity against pentylenetetrazol (PTZ) was assessed. After intraperitoneal (i.p.) injection, both dihydropyridines achieved peak blood and brain concentrations in 5 min. Estimated blood and brain elimination half-lives (t1/2) of NMD (16.7 and 22.4 min) were slightly longer than those of NFD (11.2 and 14.7 min). Brain and blood concentrations correlated with both NFD (r = 0.701, p less than 0.001) and NMD (r = 0.572, p less than 0.001). Injection of the dihydropyridines as a suspension (Tween 80) did not alter brain penetration, although systemic absorption was more erratic. NFD (p less than 0.001), NMD (p less than 0.02), and carbamazepine (CBZ, p less than 0.001) i.p. inhibited PTZ-induced seizures. Brain concentrations of PTZ were not altered by NFD pretreatment. Combining NFD and CBZ was less effective than giving NFD alone (p less than 0.005). NFD (p less than 0.002) and NMD (p less than 0.001) inhibited PTZ seizures after 2-week oral dosing, but low dosing was more effective than high dosing (p less than 0.002). NFD and NMD cross the blood-brain barrier (BBB) in mice and inhibit PTZ seizures. A possible therapeutic window was identified, and NFD and CBZ were less effective in combination than singly. A pharmacodynamic interaction may exist, inhibiting effective use of dihydropyridines as adjunctive therapy in epileptic patients.     

二氢吲哚类化合物的合成及其抑酶活性

本文报道了一系列二氢吲哚衍生物的合成,并测定其抑制胆碱酯酶活性,发现二氢吲哚环被二氢吲哚酮结构所取代,3位季碳被仲碳原子所取代,5位以可能有抑制酶活性的环磷酰基或磺酰基代替二甲氨甲酰基,均使抑酶活性几乎完全消失。在合成过程中,使1位N-烃化或5位O-酰化选择性地进行。