A comparative study of vigabatrin vs. carbamazepine in monotherapy of newly diagnosed partial seizures in children

Carbamazepine (CBZ) is a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children. Vigabatrin (VGB) is a relatively new second line antiepileptic drug and was first registered for use in Poland more than ten years ago. Few reports have been published on the comparison of efficacy of VGB in children with epilepsy. The objective of this study is to evaluate the safety, efficacy and EEG effects of initial VGB monotherapy compared with initial CBZ monotherapy in children with newly diagnosed epilepsy. We present results of a prospective, outpatient and open study carried out in the University Hospital Center in Bia?ystok. Twenty-six children with partial epilepsy treated with VGB and 28 patients treated with CBZ were studied. The evaluation of the efficacy of the two drugs did not reveal any significant differences. Very good (reduction > 75%) seizure control was achieved in 22 out of 26 patients (84.6%) in the VGB group. One patient had a 50-75% decrease of seizures (good effect), similarly one child had a 25-50% reduction of seizures (mild effect). In two patients, we observed increased seizures (myoclonic jerks). Very good seizure control was achieved in 17 out of 28 patients (60.7%) in the CBZ group. Good seizure control was achieved in 5 out of 28 patients (17.8%) and mild control was seen in two children. No improvement was observed in 4 (14%) of the patients. The EEG background activity was improved in VGB-treated patients. No effect on the EEG background activity was observed in CBZ-treated children. VGB seems to be a safe and effective antiepileptic drug as primary monotherapy for epilepsy in children with similar proportion of side effects as CBZ.     

Preliminary observations on the activity of progabide, administered as monotherapy in complex partial seizures

Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.     

Allopurinol does not affect the anticonvulsant activity of carbamazepine and valproate in maximal electroshock-induced convulsions in mice

Allopurinol, an inhibitor of xanthine oxidase, is indicated in the management of patients with elevated serum and urinary uric acid levels. It was also reported to be beneficial in patients with epilepsy when added to traditional antiepileptic drug. Here, we investigated the effect of allopurinol upon the electrical seizure threshold and its effect on the protective efficacy of common antiepileptic drugs, carbamazepine (CBZ) and valproate (VPA) against maximal electroshock (MES)-induced convulsions in mice. We found that allopurinol administered at doses of 5, 15 or 45 mg/kg, did not affect electrical seizure threshold. When administered acutely or for a prolonged period of time (5 times every 24 h), it did not affect anticonvulsant activity of CBZ and VPAin MES. Free plasma concentration of both anticonvulsants was not affected by allopurinol given at a dose of 45 mg/kg for 5 days. Thus, our results did not support suggestions that allopurinol can be beneficial as add-on drug in the management of epilepsy at least in patients treated with CBZ or VPA.     

Influence of salbutamol on the anticonvulsant potency of the antiepileptic drugs in the maximal electroshock-induced seizures in mice

Backgroundβ₂-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β₂-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures.MethodsSeizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals’ motor coordination and memory processes was also evaluated.ResultsSingle SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β₂-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals’ motor performance and memory after both single and 7 days administration.ConclusionsPresented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β₂-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.     

A multicenter, placebo-controlled, double-blind study of efficacy of a new form of carbamazepine (Carbatrol) in refractory epileptic patients

Carbatrol (CBR) is a new multiple-unit, sustained-release dosage form of carbamazepine (CBZ) developed by Pharmavene. We present a multicenter, outpatient, randomized, double-blind parallel group study (No PI 101) carried out in two centers in Poland. CBR was evaluated in 47 patients with uncontrolled partial onset seizures. During the 28-day baseline period, patients were required to have at least two seizures and to take CBZ at a therapeutic level, a second antiepileptic drug was allowed but not valproic acid (VPA ). Patients were randomized to VPA or to CBR (dosages 800, 1200, 1600 mg/day). Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in 2-day seizure frequency, two-fold increase in weekly seizure frequency, single generalized tonic-clonic seizure (GTCs) if none occurred during baseline or prolongation of GTCs. The primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPAand 7 on CBR met escape criteria. CBR adverse experiences were all mild or moderate in severity. CBR therapy was effective in the treatment of partial complex seizures with or without generalization.     

Histamine and selective H3-receptor ligands: a possible role in the mechanism and management of epilepsy.

The interaction of selective histamine H3-receptor agonist R(alpha)-methyl-histamine (RAMH) and antagonist thioperamide (THP) with some antiepileptic drugs [AED; phenytoin (PHT), carbamazepine (CBZ), sodium valproate (SVP), and gabapentin (GBP)] was studied on seizures induced by maximal electroshock (MES) and pentylenetetrazole (PTZ) in mice. It was found that subeffective dose of THP in combination with the subeffective doses of PHT and GBP provided protection against MES and/or PTZ-induced seizures. Further, RAMH reversed the protection afforded by either PHT or GBP on MES and/or PTZ seizures. In another set of experiments, the histamine content was measured in the whole brain and in different brain regions including cerebral cortex, hypothalamus, brain stem and cerebellum following convulsant (MES and PTZ) and AED treatment. It was seen that while MES exhibited a tendency to enhance brain histamine levels, PTZ showed the opposite effect. AEDs either increased (PHT and GBP) or decreased (SVP) brain histamine content in different regions to varying degrees. The results indicate a role for histamine in seizures and in the action of AEDs and suggest that selective H3-receptor antagonists may prove to be of value as adjuncts to conventional AEDs.     

Gabapentin and lamotrigine: novel antiepileptic drugs.

The pharmacokinetics, efficacy, and adverse effects of gabapentin and lamotrigine, two new antiepileptic drugs (AEDs), are reviewed. Gabapentin and lamotrigine are promising advances in the treatment of epilepsy, which has not been satisfactorily controlled by available agents in 25-41% of patients. Gabapentin is chemically similar to gamma-aminobutyric acid, but it is able to pass into the central nervous system. It is effective for the treatment of partial-onset seizures that are refractory to other AEDs. It has no known drug-drug interactions and a relatively benign adverse effect profile, but its short half-life necessitates at least thrice-daily dosing. Lamotrigine is structurally unrelated to the other available AEDs. Its role is currently limited to add-on therapy in patients with partial seizures, with or without secondary generalization, that are resistant to current treatment. The efficacy of lamotrigine in patients with primary generalized tonic-clonic seizures, absence seizures, and Lennox-Gastaut syndrome remains to be validated. The adverse effect profile also remains to be determined. A rash may appear in up to 5% of patients, possibly necessitating discontinuation of the drug. Although lamotrigine does not seem to affect the pharmacokinetics of the other AEDs, the other AEDs affect lamotrigine pharmacokinetics. Lamotrigine can be given once or twice daily. Gabapentin and lamotrigine may be useful in treating patients whose epilepsy is not controlled by other available AEDs; however, further research is needed to confirm their roles in epilepsy treatment.     

Safety issues around misuse of antiepileptics

Introduction: Drug misuse is a deliberate or accidental (by omission) nonadherence to medical recommendations, which may range from inappropriate use (missed, increased, or lowered doses or even complete discontinuation of therapy) to compulsive overdosing. Currently, this phenomenon affects as many as 20 – 80% of epileptic patients.

Areas covered: Long-standing research has enabled the identification and understanding of factors behind the phenomenon of nonadherence to medical recommendations. An inappropriate use of antiepileptic drugs usually has serious health implications for both children and adults. These involve increased frequency of seizures in patients who lower their doses or discontinue therapy, which may often lead to pathologies. On the other hand, patients who increase or take extra doses expose themselves to toxic effects of antiepileptic drugs. In both cases, there is an increased need for hospitalization, which further implies extra healthcare costs. The most misused antiepileptic drug is gabapentin (53%), whereas the least misused are lamotrigine, levetiracetam, and phenytoin (all drugs at 32%).

Expert opinion: The prevalence of misuse of antiepileptic drugs among epileptic patients is comparable to that observed in other chronically ill individuals. Preventive strategies have to be based on the reasons leading to nonadherence.     

Zonisamide: review of its use in epilepsy therapy

Zonisamide is an antiepileptic drug used as adjunctive therapy for refractory partial seizures in adults. Because of the multiple mechanisms of action, it shows a broad spectrum of anticonvulsant activity and has been effective in several types of seizures, including partial and generalized seizures, tonic-clonic seizures and absence seizures in patients unresponsive to other anticonvulsants. Myoclonic epilepsy, Lennox-Gastaut syndrome and infantile spasms have also been treated effectively with zonisamide. Recent clinical studies have demonstrated additional potential for therapeutic use in neuropathic pain, bipolar disorder, migraine, obesity, eating disorders and Parkinson's disease. Despite adverse events, zonisamide is relatively safe and well tolerated in patients, and shows low discontinuation rate. It has a good pharmacokinetic profile and a low drug interaction potential. Zonisamide is considered as a drug that effectively reduces the frequency of partial seizures.     

Efficacy and Tolerability of Antiepileptic Drugs in Patients with Focal Epilepsy: Systematic Review and Network Meta‐analyses

Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy. In addition, we compared CBZ with other AEDs for the monotherapy of focal epilepsy. We performed a search of the MEDLINE/PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for randomized controlled clinical trials. To compare the relative efficacy and tolerability of the AEDs, we performed network meta‐analyses using a Bayesian random‐effects model. Sensitivity analyses were conducted to determine the robustness of the results. A total of 65 studies were included in this review, composing 16,025 patients. Clobazam, levetiracetam, lamotrigine, oxcarbazepine, sulthiame, topiramate, and valproate had the best efficacy profiles and demonstrated no evidence of superiority or inferiority compared with CBZ. However, CBZ showed the greatest risk of patient discontinuation due to intolerable adverse reactions, whereas lamotrigine had the best safety profile and an 81% probability of being the best for the tolerability outcome of patient withdrawals from the study due to intolerable adverse reactions, followed by sulthiame (60%) and clobazam (51%). The newer AEDs—levetiracetam, lamotrigine, oxcarbazepine, sulthiame, and topiramate—should be considered for monotherapy of focal epilepsy because they were demonstrated to be as effective as the older ones (CBZ, clobazam, and valproate) for the treatment of focal epilepsy and were more tolerable. Lamotrigine was the AED with the best tolerability profile, suggesting that it may be the best option for the treatment of focal epilepsy in children and adults.     

Lamotrigine. A review of its use in childhood epilepsy

Lamotrigine is an antiepileptic agent that blocks use-dependent voltage-sensitive sodium channels, thereby preventing excitatory neurotransmitter release. However, this mechanism does not explain the broad range of clinical efficacy of this agent. In noncomparative trials, adjunctive lamotrigine (< or = 15 mg/kg/day) improved seizure control in children and adolescents with various refractory seizure types, with about 29 to 90% of patients showing a > or = 50% reduction in seizure frequency after > or = 3 months' treatment. Lamotrigine was particularly effective in generalised seizures, especially absence seizures and those related to the Lennox-Gastaut syndrome. In one placebo-controlled study, 33% of children and young adults (aged 3 to 25 years) with refractory Lennox-Gastaut syndrome had a reduction in seizure frequency of > or = 50% after 16 weeks of adjunctive lamotrigine treatment, compared with 16% of placebo recipients (p = 0.01). Significant reductions in seizure frequency when compared with placebo were also observed in patients with refractory generalised and partial seizures. The use of lamotrigine has also been associated with beneficial effects on cognition and behaviour. Adverse events associated with lamotrigine are primarily neurological, gastrointestinal and dermatological and are typically mild or moderate and transient with the exception of a potentially serious rash. Maculopapular or erythematous skin rash occurred in approximately 12% of paediatric patients (aged < 16 years) treated with lamotrigine and was the most common reason for treatment discontinuation. More severe forms of rash, including Stevens-Johnson syndrome, occasionally occurred, with a 3-fold higher incidence in children (approximately 1%) than adults (approximately 0.3%). However, lamotrigine treatment in paediatric trials was generally given at higher initial doses and faster dose escalations than recently revised recommendations. These factors, as well as concomitant use of valproic acid (valproate sodium), are associated with an increased risk of rash. CONCLUSION: Although published clinical evidence is still limited in paediatric populations, lamotrigine is an effective and generally well tolerated broad-spectrum agent for adjunctive treatment of refractory seizures in children, most notably in those with Lennox-Gastaut syndrome. Results of direct comparisons with other antiepileptic agents are needed to determine more clearly the place of lamotrigine, particularly relative to newer agents, in the treatment of childhood epilepsy. The potential for serious rash in recipients of lamotrigine should also be kept in mind. Nonetheless, lamotrigine is a welcome addition to the available treatments for refractory childhood epilepsy, particularly Lennox-Gastaut syndrome.     

Levetiracetam: a novel antiepileptic drug.

Levetiracetam is a new antiepileptic drug, structurally and mechanistically dissimilar to other marketed antiepileptic drugs. It is effective in reducing partial seizures in patients with epilepsy, both as adjunctive treatment and as monotherapy. Levetiracetam has many therapeutic advantages for patients with epilepsy. It has favorable pharmacokinetic characteristics (good bioavailability, linear pharmacokinetics, insignificant protein binding, lack of hepatic metabolism, and rapid achievement of steady-state concentrations) and a low potential for drug interactions. Recommended starting dosages are considered to be clinically effective; therefore, patients can have some protection from seizures soon after they begin levetiracetam. The most common adverse effects observed with levetiracetam are mild and include somnolence, asthenia, and dizziness. Clinical experience and data from meta-analyses indicate that levetiracetam is well tolerated, with efficacy comparable or slightly better than that observed with other new antiepileptic drugs. Levetiracetam may be particularly useful in patients who are unresponsive to other antiepileptic drugs, patients receiving drugs with increased potential for drug interactions, or those with hepatic impairment.     

Neuronal MDR-1 gene expression and persistent low levels of anticonvulsants in a child with refractory epilepsy

SUMMARY: It is estimated that 20-25% of epileptic patients fail to achieve good control with antiepileptic drug (AED) treatment; thus, refractory epilepsy (RE) has been described in patients who have adequate therapeutic levels of AEDs without control of seizures. Multidrug resistance genes have been reported to be highly expressed in brain of patients with RE. Persistent low plasma levels of AEDs and high brain expression of the multidrug resistance product P-glycoprotein (P-gp) have been previously communicated in a case report of RE secondary to tuberous sclerosis. Here, the authors report a case of an 8-year-old boy diagnosed with partial RE with focal seizures who was admitted to hospital for a severe episode of subintrant crisis. The patient received polytherapy with carbamazepine (CBZ), phenytoin (PHT), and valproic acid (VA); however, habitual doses of these AEDs failed to control the patient's symptoms. AED blood levels were monitored for 25 consecutive days and showed low values in 8/25 (33%) for CBZ, 10/25 (40%) for PHT, and 25/25 (100%) for VA of samples studied. Because the patient developed focal status epilepticus, surgical treatment by callosotomy was done, resulting in a significant improvement in epileptic symptoms. The immunostaining of brain specimens showed significantly increased expression of P-gp not only in vascular endothelial cells and related astrocytes but also in neurons. Overexpression of P-gp in the brain does not explain the low blood levels of AEDs described in these cases. Different mechanisms such as drug-drug interactions and drug transporters can be involved in the results observed. The P-gp overexpression and/or its pharmacologic induction should be considered as a potential mechanism responsible for drug resistance to epilepsy treatment and highly suspected in patients with persistent subtherapeutic AEDs plasma levels.     

341 例癫痫患儿用药特点分析

目的：探讨癫痫患儿临床用药特点,为临床合理应用抗癫痫药物提供参考。方法：回顾性分析2018年2月至2018年8月西北妇女儿童医院和西安交通大学第二附附属医院收治的341例癫痫患儿临床资料,对其用药方案选择及发作控制率进行统计分析。结果：341例癫痫患儿中,男女比例1.04∶1,年龄9个月~19岁,其中1~3岁患儿占比最大,为32.55%。经抗癫痫药物治疗,341例患儿Ⅲ级以上总体发作控制率为84.45%。单药治疗、双药治疗和三种及以上联合治疗Ⅱ级以上控制率分别为94.45%、69.63%和45.56%。单药治疗中使用率前3位的药物分别为左乙拉西坦、苯巴比妥和卡马西平;多药治疗中使用率前3位的药物分别为左乙拉西坦、丙戊酸钠和托吡酯。单药治疗以左乙拉西坦为主,联合治疗主要以左乙拉西坦＋丙戊酸钠或托吡酯为主。结论：儿童癫痫发病以婴幼儿期最多,药物治疗总体控制率较高,新型抗癫痫药和传统抗癫痫药在治疗选择中使用率相当,新型抗癫痫药物左乙拉西坦在各发作类型及各种治疗方案中使用率最高。治疗药物选择主要为左乙拉西坦、苯巴比妥和卡马西平,抗癫痫药物联合治疗方案主要为丙戊酸钠+左乙拉西坦和丙戊酸钠+氯硝西泮+左乙拉西坦。     

Cytokines, epilepsy and epileptic drugs--is there a mutual influence?

In recent years, the functional disturbances of the immune system, both humoral and cell-mediated immunity, have been detected more often among persons with epilepsy than in general population. A number of irregularities in cytokine production have been found in epileptic patients. It shows that epileptic seizures stimulate, per se, synthesis of pro-inflammatory and pro-convulsive cytokines. Some antiepileptic drugs (AEDs) influence the production of cytokines, too. The influence of AEDs on cytokine concentrations in blood has been observed, e.g. during carbamazepine (CBZ) or valproic acid (VPA) therapy. This article is a review of the literature which focuses on the connections between epilepsy and the cytokine system as well as on the influence of AEDs on the cell-mediated and humoral response in epileptic patients. Correlation of immunological irregularities in patients with the type, dosage, and serum level of AEDs will allow for early detection of undesirable treatment consequences in epilepsy. Elucidation of connections between cytokine system, epileptogenesis and effectiveness of AED therapy requires a better planned research on larger groups of patients with epilepsy.     

Gabapentin synergistically interacts with topiramate in the mouse maximal electroshock seizure model: an isobolographic analysis

The anticonvulsant effects produced by topiramate (TPM) and gabapentin (GBP)--two second-generation antiepileptic drugs, in numerous fixed-ratio combinations of 8:1, 4:1, 2:1, 1:1, 1:2, 1:4 and 1:8 were examined by isobolographic analysis in the mouse maximal electroshock seizure (MES) model. Results indicate that the combinations of TPM and GBP at the fixed-ratios of 2:1, 1:1, 1:2, 1:4 and 1:8 resulted in supra-additive (synergistic) interaction against MES-induced seizures. Moreover, the combinations of TPM and GBP (at their median effective doses) did not affect motor performance of animals challenged with the chimney test and had no impact on neuromuscular tone in the grip-strength test. Additionally, GBP had no impact on total brain TPM concentrations, and simultaneously, TPM did not alter brain GBP concentrations, indicating that the interaction between drugs was pharmacodynamic in nature. In conclusion, supra-additive interaction of TPM with GBP against MES-induced seizures, lack of motor coordination and neuromuscular tone impairments as well as lack of pharmacokinetic interactions between TPM and GBP in preclinical study, strongly support the combined application of both antiepileptic drugs in patients with refractory partial epilepsy.     

Progesterone therapy in women with epilepsy

BackgroundProgesterone with its anti-seizure effect plays a role in the pathophysiology of catamenial epilepsy which affects 31–60% of epileptic women. In this study, an attempt to treat women suffering from catamenial epilepsy with progesterone, as an adjuvant drug, was made.MethodsThe treatment was given to 36 women aged 20–40 years (mean age: 30.75 ± 6.05) with seizures in the entire second half of the menstrual cycle, who were found to have low serum levels of progesterone on days 22, 27, 28 of the cycle in comparison with a control group of healthy women. The patients were administered progesterone in a daily dose of 50 mg on days 16–25 of each cycle. The serum levels of antiepileptic drugs were assayed. The period of progesterone therapy ranged from 3 to 45 months (17.7 on average).ResultsThree patients were free of secondary generalized seizures, and one – of simple partial seizures. Adecline in the frequency of primary and secondary generalized seizures by 20–96% (55.9% on average) was accomplished in 18 patients (primary generalized by 20–96% – 54.7% on average, and secondarily generalized by 38–85% – 59% on average).Adecline in the frequency of complex partial seizures by 38–87% (63.1% on average) was achieved in 15 women. In 1 patient, the frequency of myoclonic seizures decreased by 46%. There was no improvement in 5 women (3 patients with generalized, 1 with complex partial and 1 with simple partial seizures). An exacerbation of seizure frequency occurred in 5 patients. Adverse effects were not found in any of the subjects. The average concentrations of antiepileptic drugs during hormonal therapy were in the therapeutic range.ConclusionProgesterone combined with antiepileptic therapy was well tolerated and resulted in a significant reduction of seizure frequency in majority of patients with catamenial epilepsy.     

Evaluation of anticonvulsants for possible use in neuropathic pain

Neuropathic pain is a kind of pain related with functional abnormality of neurons. Despite large progress in pharmacotherapy, neuropathic pain is still considered an unmet need. Nowadays, there are few drugs registered for this condition, such as pregabalin, gabapentin, duloxetine, carbamazepine, and lidocaine. Among them, pregabalin, gabapentin and carbamazepine are well known antiepileptic drugs. Among the group of new antiepileptic drugs, which are addressed to 1% of human world population suffering from seizures, it turned out that 30% of the seizures resistant to pharmacotherapy has not enough market to justify the costs of drug development. Therefore, it is already a phenomenon that researchers turn their projects toward a larger market, related with possible similar mechanism. Anticonvulsant mechanism of action is in the first place among primary indications for drugs revealing potential analgesic activity. Therefore, many drug candidates for epilepsy, still in preclinical stage, are being evaluated for activity in neuropathic pain. This review is focusing on antiepileptic drugs, which are evaluated for their analgesic activity in major tests related with neuropathic pain. Relation between structure, mechanism of action and result in tests such as the Chung model (spinal nerve ligation SNL), the Bennett model (chronic constriction injury of sciatic nerve CCI) and other tests are considered. The first examples are carbamazepine, gabapentin, and lacosamide as drugs well established in epilepsy market as well as drug candidates such as valnoctamide, and other valproic acid derivatives, novel biphenyl pyrazole derivatives, etc. Moreover, clinical efficacy related with listed animal models has been discussed.     

Potentiation of clobazam's anticonvulsant activity by etifoxine, a non-benzodiazepine tranquilizer, in mice. Comparison studies with sodium valproate

The interaction of two tranquilizers, the 1,5-benzodiazepine clobazam (CBZ, Frisium) and the non-benzodiazepine etifoxin (Hoe-36,801) hydrochloride (EFX, 6-chloro-2-ethylamino-4-methyl-4-phenyl-4H-3,1-benzoxazine HCl) was investigated for anticonvulsant activity in mice. Corresponding experiments were performed with the antiepileptic drug sodium valproate (VPA). Tonic-clonic (maximal) seizures were induced by maximal electroshock (MES; 12 mA, 200 ms) and clonic (threshold) seizures by pentetrazol (PTZ; 85 mg/kg s.c.). The addition of an anticonvulsant threshold dose of EFX (50 mg/kg p.o.) led to an increase of CBZ's potency against both MES- and PTZ-seizures by 410 or 450%, respectively. Under the same conditions, EFX enhanced the potency of VPA only by 20 or 80% and a threshold dose of VPA (100 mg/kg p.o.) enhanced the potency of CBZ by 110 or 0%, respectively. It is concluded that this potentiation of CBZ's anticonvulsant activity by EFX may be beneficially used in epileptic patients either to increase CBZ's antiepileptic effects or to reduce CBZ's therapeutic doses in order to prevent or delay the development of resistance.     

加巴喷丁胶囊添加治疗癫痫的临床疗效和安全性

目的 :评价国产加巴喷丁的临床疗效和安全性。方法 :采用多中心、双盲、安慰剂对照、平行试验方法观察加巴喷丁添加治疗癫痫部分性发作(PS)和泛化性全身强直 阵挛发作 (SGTCS) 2 4wk。分 2组 :加巴喷丁组 (原基础抗癫痫药 +加巴喷丁胶囊 90 0mg·d- 1) 110例 ,对照组 (原基础抗癫痫药 +安慰剂 ) 10 8例。结果 :加巴喷丁组总有效率5 2 .7% (5 8/ 110 ) ,对照组 31.5 % (34/ 10 8) ,2组比较 ,P <0 .0 1;2组基线期发作次数≥ 4次 (2 8d)病人的疗效比较 ,P <0 .0 5 ;不同发作类型的疗效比较SGTCS >复杂部分性发作 (CPS) >简单部分性发作(SPS) (P <0 .0 1) ;2组痫样放电减少≥ 2 5 %的疗效比较 ,P <0 .0 5。2组不良反应发生率比较差异无显著性 (P >0 .0 5 )。结论 :国产加巴喷丁添加治疗对控制癫痫PS和SGTCS是有效而安全的。