癫痫药物治疗的过去、现在与未来

doi:10.3969/j.issn.1672-6731.2023.02.002

摘要/Abstract

摘要： 癫痫是临床常见的神经系统疾病，发病机制尚未阐明，抗癫痫发作药物是主要治疗方法，其本质是抗癫痫发作而非改善癫痫疾病。本文依照“过去”、“现在”、“未来”的时间顺序，从药代动力学、药理学机制、适应证、疗效、不良反应等方面综述抗癫痫发作药物的发展历程并展望未来发展方向，为癫痫的预防与治疗提供依据。

关键词: 癫痫, 抗惊厥药, 医学史, 综述

Abstract: Epilepsy is a common clinical neurological disease, the pathogenesis of which has not yet been elucidated. As the main treatment, antiepileptic seizure medicine (ASM) fights against seizures rather than improve epilepsy. According to the chronological order of "past", "present" and "future", this article reviews the development history of ASM from the aspects of pharmacokinetics, pharmacological mechanism, indications, efficacy and adverse reactions, and looks forward to the future development direction. It can provide a theoretical basis for the prevention and treatment of epilepsy.

Key words: Epilepsy, Anticonvulsants, History of medicine, Review

史向松, 宋苏蒙, 徐建洋. 癫痫药物治疗的过去、现在与未来[J]. 中国现代神经疾病杂志, 2023, 23(2): 78-88.

SHI Xiang-song, SONG Su-meng, XU Jian-yang. The past, present and future of drug therapy for epilepsy[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2023, 23(2): 78-88.

http://journal11.magtechjournal.com/cjcnn/CN/Y2023/V23/I2/78

参考文献

[1] Naimo GD, Guarnaccia M, Sprovieri T, Ungaro C, Conforti FL, Andò S, Cavallaro S. A systems biology approach for personalized medicine in refractory epilepsy[J]. Int J Mol Sci, 2019, 20:3717.
[2] Chen Z, Brodie MJ, Kwan P. What has been the impact of new drug treatments on epilepsy[J]? Curr Opin Neurol, 2020, 33:185-190.
[3] Janmohamed M, Brodie MJ, Kwan P. Pharmacoresistance:epidemiology, mechanisms, and impact on epilepsy treatment[J]. Neuropharmacology, 2020, 168:107790.
[4] Perucca E, Brodie MJ, Kwan P, Tomson T. 30 years of second-generation antiseizure medications:impact and future perspectives[J]. Lancet Neurol, 2020, 19:544-556.
[5] Porter RJ, Dhir A, Macdonald RL, Rogawski MA. Mechanisms of action of antiseizure drugs[J]. Handb Clin Neurol, 2012, 108:663-681.
[6] Lattanzi S, Zaccara G, Giovannelli F, Grillo E, Nardone R, Silvestrini M, Trinka E, Brigo F. Antiepileptic monotherapy in newly diagnosed focal epilepsy:a network meta-analysis[J]. Acta Neurol Scand, 2019, 139:33-41.
[7] Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug resistance in epilepsy:clinical impact, potential mechanisms, and new innovative treatment options[J]. Pharmacol Rev, 2020, 72:606-638.
[8] Löscher W, Klein P. The pharmacology and clinical efficacy of antiseizure medications:from bromide salts to cenobamate and beyond[J]. CNS Drugs, 2021, 35:935-963.
[9] Friedlander WJ. The history of modern epilepsy:the beginning 1865-1914[M]. Westport:Greenwood Press, 2001.
[10] Strzelczyk A, Schubert-Bast S. A practical guide to the treatment of Dravet syndrome with anti-seizure medication[J]. CNS Drugs, 2022, 36:217-237.
[11] Schubert-Bast S, Wolff M, Wiemer-Kruel A, von Spiczak S, Trollmann R, Reif PS, Pritchard C, Polster T, Neubauer BA, Mayer T, Macdonald D, Kurlemann G, Kluger G, Klein KM, Kieslich M, Kay L, Kalski M, Irwin J, Herting A, Carroll J, Bettendorf U, Bast T, Rosenow F, Strzelczyk A. Seizure management and prescription patterns of anticonvulsants in Dravet syndrome:a multicenter cohort study from Germany and review of literature[J]. Epilepsy Behav, 2019, 98(Pt A):88-95.
[12] Kumbier E, Haack K. Alfred Hauptmann:the fate of a German neurologist of Jewish origin[J]. Fortschr Neurol Psychiatr, 2002, 70:204-209.
[13] Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, Kuperman R, Harbert MJ, Michelson D, Joe P, Wang S, Rismanchi N, Le NM, Mower A, Kim J, Battin MR, Lane B, Honold J, Knodel E, Arnell K, Bridge R, Lee L, Ernstrom K, Raman R, Haas RH; NEOLEV2 Investigators. Levetiracetam versus phenobarbital for neonatal seizures:a randomized controlled trial[J]. Pediatrics, 2020, 145:e20193182.
[14] Shorvon SD. Drug treatment of epilepsy in the century of the ILAE:the first 50 years, 1909-1958[J]. Epilepsia, 2009, 50 Suppl 3:69-92.
[15] Bresnahan R, Martin-McGill KJ, Milburn-McNulty P, Powell G, Sills GJ, Marson AG. Sulthiame add-on therapy for epilepsy[J]. Cochrane Database Syst Rev, 2019, 8:CD009472.
[16] Brigo F, Igwe SC, Lattanzi S. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents[J]. Cochrane Database Syst Rev, 2021, 1:CD003032.
[17] Shorvon SD. Drug treatment of epilepsy in the century of the ILAE:the second 50 years, 1959-2009[J]. Epilepsia, 2009, 50 Suppl 3:93-130.
[18] Caraballo RH, Reyes Valenzuela G, Fortini S, Espeche A, Gamboni B, Bautista C, Cachia P, Semprino M, Gallo A, Galicchio S. Use of sulthiame as add-on therapy in children with myoclonic atonic epilepsy:a study of 35 patients[J]. Epilepsy Behav, 2022, 131(Pt A):108702.
[19] Dao K, Thoueille P, Decosterd LA, Mercier T, Guidi M, Bardinet C, Lebon S, Choong E, Castang A, Guittet C, Granier LA, Buclin T. Sultiame pharmacokinetic profile in plasma and erythrocytes after single oral doses:a pilot study in healthy volunteers[J]. Pharmacol Res Perspect, 2020, 8:e00558.
[20] Shorvon SD, Weiss G, Avanzini G, Engel J, Meinardi H, Moshe S, Reynolds E, Wolf P. International League Against Epilepsy (ILAE) 1909-2009:a centenary history[M]. New York:Wiley-Blackwell, 2009.
[21] Sills GJ, Rogawski MA. Mechanisms of action of currently used antiseizure drugs[J]. Neuropharmacology, 2020, 168:107966.
[22] Riikonen R. Infantile spasms:outcome in clinical studies[J]. Pediatr Neurol, 2020, 108:54-64.
[23] Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, Devinsky O, Cross JH, Guerrini R, Talwar D, Miller I, Farfel G, Galer BS, Gammaitoni A, Mistry A, Morrison G, Lock M, Agarwal A, Lai WW, Ceulemans B; FAiRE DS Study Group. Fenfuramine hydrochloride for the treatment of seizures in Dravet syndrome:a randomised, double-blind, placebo-controlled trial[J]. Lancet, 2019, 394:2243-2254.
[24] Nabbout R, Mistry A, Zuberi S, Villeneuve N, Gil-Nagel A, Sanchez-Carpintero R, Stephani U, Laux L, Wirrell E, Knupp K, Chiron C, Farfel G, Galer BS, Morrison G, Lock M, Agarwal A, Auvin S; FAiRE, DS Study Group. Fenfluramine for treatment-resistant seizures in patients with Dravet syndrome receiving stiripentol-inclusive regimens:a randomized clinical trial[J]. JAMA Neurol, 2020, 77:300-308.
[25] Goh KK, Chang SC, Chen CH, Lu ML. Therapeutic strategies for treatment-resistant depression:state of the art and future perspectives[J]. Curr Pharm Des, 2020, 26:244-252.
[26] Ondo WG. Current and emerging treatments of essential tremor[J]. Neurol Clin, 2020, 38:309-323.
[27] Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennell P, Thomas SV. Executive summary:management of epilepsy in pregnancy:a report from the International League against Epilepsy Task Force on Women and Pregnancy[J]. Epilepsia, 2019, 60:2343-2345.
[28] Sen A, Jette N, Husain M, Sander JW. Epilepsy in older people[J]. Lancet, 2020, 395:735-748.
[29] Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs:a 30-year longitudinal cohort study[J]. JAMA Neurol, 2018, 75:279-286.
[30] Verrotti A, Lattanzi S, Brigo F, Zaccara G. Pharmacodynamic interactions of antiepileptic drugs:from bench to clinical practice[J]. Epilepsy Behav, 2020, 104(Pt A):106939.
[31] Pisani F, Oteri G, Russo MF, Di Perri R, Perucca E, Richens A. The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures:evidence for a pharmacodynamic interaction[J]. Epilepsia, 1999, 40:1141-1146.
[32] Gayatri NA, Livingston JH. Aggravation of epilepsy by anti-epileptic drugs[J]. Dev Med Child Neurol, 2006, 48:394-398.
[33] Jafarpour S, Hirsch LJ, Gaínza-Lein M, Kellinghaus C, Detyniecki K. Seizure cluster:definition, prevalence, consequences, and management[J]. Seizure, 2019, 68:9-15.
[34] Gidal B, Klein P, Hirsch LJ. Seizure clusters, rescue treatments, seizure action plans:unmet needs and emerging formulations[J]. Epilepsy Behav, 2020, 112:107391.
[35] Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT. Medical genetics:a marker for Stevens-Johnson syndrome[J]. Nature, 2004, 428:486.
[36] Xu JY, Guan XN. Analysis of 31 cases with hypersensitivity syndrome with antiepileptic drugs[J]. Zhonghua Shen Jing Ke Za Zhi, 2004, 37:543-544[.徐建洋, 管学能. 抗癫药高度敏感综合征31例分析[J]. 中华神经科杂志, 2004, 37:543-544.]
[37] Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver:ways out of the current dilemma[J]. Epilepsia, 2011, 52:657-678.
[38] Brigo F, Lattanzi S, Igwe SC, Behzadifar M, Bragazzi NL. Zonisamide add-on therapy for focal epilepsy[J]. Cochrane Database Syst Rev, 2020, 7:CD001416.
[39] Aslan M, Gungor S. Effectiveness of zonisamide in childhood refractory epilepsy[J]. Childs Nerv Syst, 2022, 38:971-976.
[40] Tarquinio D, Dlugos D, Wheless JW, Desai J, Carrazana E, Rabinowicz AL. Safety of diazepam nasal spray in children and adolescents with epilepsy:results from a long-term phase 3 safety study[J]. Pediatr Neurol, 2022, 132:50-55.
[41] Wheless JW. A critical evaluation of midazolam nasal spray for the treatment of patients with seizure clusters[J]. Expert Rev Neurother, 2021, 21:1195-1205.
[42] Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN Investigators. Randomized trial of three anticonvulsant medications for status epilepticus[J]. N Engl J Med, 2019, 381:2103-2113.
[43] Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, Rogers A, Barsan W, Cloyd J, Lowenstein D, Bleck TP, Conwit R, Meinzer C, Cock H, Fountain NB, Underwood E, Connor JT, Silbergleit R; Neurological Emergencies Treatment Trials, Pediatric Emergency Care Applied Research Network investigators. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT):a double-blind, responsive-adaptive, randomised controlled trial[J]. Lancet, 2020, 395:1217-1224.
[44] Satishchandra P, Rathore C, Apte A, Kumar A, Mandal A, Chauhan D, Agadi J, Gurumukhani J, Asokan K, Venkateshwarlu K, Lingappa L, Sundaracharya NV, Jha SK, Ravat S, Vk S, Garg S, Shah SV, Alagesan S, Razdan S, Padhy U, Agarwal VK, Arora V, Menon B, Shetty S, Chodankar D. Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes:an Indian experience[J]. Epilepsy Behav, 2022, 130:108671.
[45] Jozwiak S, Kotulska K, Wong M, Bebin M. Modifying genetic epilepsies:results from studies on tuberous sclerosis complex[J]. Neuropharmacology, 2020, 166:107908.
[46] Kotulska K, Kwiatkowski DJ, Curatolo P, Weschke B, Riney K, Jansen F, Feucht M, Krsek P, Nabbout R, Jansen AC, Wojdan K, Sijko K, Głowacka-Walas J, Borkowska J, Sadowski K, Domańska-Pakieła D, Moavero R, Hertzberg C, Hulshof H, Scholl T, Benova B, Aronica E, de Ridder J, Lagae L, Jóźwiak S; EPISTOP Investigators. Prevention of epilepsy in infants with tuberous sclerosis complex in the EPISTOP trial[J]. Ann Neurol, 2021, 89:304-314.
[47] Marson A, Burnside G, Appleton R, Smith D, Leach JP, Sills G, Tudur-Smith C, Plumpton C, Hughes DA, Williamson P, Baker GA, Balabanova S, Taylor C, Brown R, Hindley D, Howell S, Maguire M, Mohanraj R, Smith PE; SANAD Ⅱ collaborators. The SANAD Ⅱ study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy:an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial[J]. Lancet, 2021, 397:1375-1386.
[48] Panebianco M, Bresnahan R, Ramaratnam S, Marson AG. Lamotrigine add-on therapy for drug-resistant focal epilepsy[J]. Cochrane Database Syst Rev, 2020, 3:CD001909. A, Stern R.
[49] Rzany B, Correia O, Kelly JP, Naldi L, Auquier Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis during first weeks of antiepileptic therapy:a case-control study:study group of the International Case Control Study on Severe Cutaneous Adverse Reactions[J]. Lancet, 1999, 353:2190-2194.
[50] Fujii K, Okayasu H, Shinozaki T, Shimoda K, Ozeki Y. Slower titration of lamotrigine reduces the risk of rash[J]. Psychiatry Clin Neurosci, 2020, 74:282-283.
[51] Jang Y, Moon J, Kim N, Kim TJ, Jun JS, Shin YW, Chang H, Kang HR, Lee ST, Jung KH, Park KI, Jung KY, Chu K, Lee SK. A new rapid titration protocol for lamotrigine that reduces the risk of skin rash[J]. Epilepsia Open, 2021, 6:394-401. JR,
[52] Hong JSW, Atkinson LZ, Al-Juffali N, Awad A, Geddes Tunbridge EM, Harrison PJ, Cipriani A. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia:systematic review, meta-analysis, and rationale[J]. Mol Psychiatry, 2022, 27:1339-1349.
[53] Besli GE, Yuksel Karatoprak E, Yilmaz S. Efficacy and safety profile of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children[J]. Epilepsy Behav, 2020, 111:107289.
[54] Boon P, Ferrao Santos S, Jansen AC, Lagae L, Legros B, Weckhuysen S. Recommendations for the treatment of epilepsy in adult and pediatric patients in Belgium:2020 update[J]. Acta Neurol Belg, 2021, 121:241-257.
[55] Thomas L, Mirza MMF, Shaikh NA, Ahmed N. Rhabdomyolysis:a rare adverse effect of levetiracetam[J]. BMJ Case Rep, 2019, 12:e230851.
[56] Wu H, Liu J, Qian F, Yang J, Wang Y, Guan S. Clinical evaluation of levetiracetam in the treatment of epilepsy[J]. J Healthc Eng, 2022:ID3789516.
[57] Panebianco M, Bresnahan R, Marson AG. Pregabalin add-on for drug-resistant focal epilepsy[J]. Cochrane Database Syst Rev, 2022, 3:CD005612.
[58] Habermehl L, Mross PM, Krause K, Immisch I, Chiru D, Zahnert F, Gorny I, Strzelczyk A, Rosenow F, Möller L, Menzler K, Knake S. Stiripentol in the treatment of adults with focal epilepsy:a retrospective analysis[J]. Seizure, 2021, 88:7-11.
[59] Arzimanoglou A, Pringsheim M, Kluger GJ, Genton P, Perdomo C, Malhotra M. Safety and efficacy of rufinamide in children and adults with Lennox-Gastaut syndrome:a post hoc analysis from Study 022[J]. Epilepsy Behav, 2021, 124:108275.
[60] Yang C, Peng Y, Zhang L, Zhao L. Safety and tolerability of lacosamide in patients with epilepsy:a systematic review and meta-analysis[J]. Front Pharmacol, 2021, 12:694381.
[61] Pozzi M, Zanotta N, Epifanio R, Baldelli S, Cattaneo D, Clementi E, Zucca C. Lacosamide effectiveness and tolerability in patients with drug-resistant epilepsy and severe disability under polytherapy:therapy optimization as emerging from an observational study[J]. Epilepsy Behav, 2022, 128:108598.
[62] Chang XC, Yuan H, Wang Y, Xu HQ, Hong WK, Zheng RY. Eslicarbazepine acetate add-on therapy for drug-resistant focal epilepsy[J]. Cochrane Database Syst Rev, 2021, 6:CD008907.
[63] Snoeren A, Majoie MHJM, Fasen KCFM, Ijff DM. Brivaracetam for the treatment of refractory epilepsy in patients with prior exposure to levetiracetam:a retrospective outcome analysis[J]. Seizure, 2022, 96:102-107.
[64] Li Y, Zeng Y, Mu J, Zhou D. The efficacy and safety of adjunctive perampanel for the treatment of refractory focal-onset seizures in patients with epilepsy:a meta-analysis[J]. Epilepsia Open, 2022, 7:271-279.
[65] Buckley CT, Waters OR, DeMaagd G. Cenobamate:a new adjunctive agent for drug-resistant focal onset epilepsy[J]. Ann Pharmacother, 2021, 55:318-329.
[66] Brandt C, Sánchez-Álvarez JC, Steinhoff BJ, Milanov I, Serratosa JM. Efficacy and safety of adjunctive cenobamate:post-hoc analysis of study C017 in patients grouped by mechanism of action of concomitant antiseizure medications[J]. Seizure, 2022, 96:86-93. G, Striano P, Russo E, Del
[67] Lattanzi S, Trinka E, Zaccara Giovane C, Silvestrini M, Brigo F. Third-generation antiseizure medications for adjunctive treatment of focal-onset seizures in adults:a systematic review and network meta-analysis[J]. Drugs, 2022, 82:199-218.
[68] Xu W, Zhang JJ. Research progress of cannabidiol in the treatment of epilepsy[J]. Shandong Di Yi Yi Ke Da Xue (Shandong Sheng Yi Xue Ke Xue Yuan) Xue Bao, 2022, 43:74-77[.徐雯, 张敬军. 大麻二酚治疗癫痫的研究进展[J]. 山东第一医科大学(山东省医学科学院)学报, 2022, 43:74-77.]
[69] Peng J, Fan M, An C, Ni F, Huang W, Luo J. A narrative review of molecular mechanism and therapeutic effect of cannabidiol (CBD)[J]. Basic Clin Pharmacol Toxicol, 2022, 130:439-456. EM, Filloux F, Kwan P, Loftus R, Sahebkar
[70] Thiele EA, Bebin F, Sparagana S, Wheless J. Long-term cannabidiol treatment for seizures in patients with tuberous sclerosis complex:an open-label extension trial[J]. Epilepsia, 2022, 63:426-439.
[71] Stockinger J, Strzelczyk A, Nemecek A, Cicanic M, Bösebeck F, Brandt C, Hamer H, Intravooth T, Steinhoff BJ. Everolimus in adult tuberous sclerosis complex patients with epilepsy:too late for success:a retrospective study[J]? Epilepsia, 2021, 62:785-794.
[72] Simon K, Sheckley H, Anderson CL, Liu Z, Carney PR. A review of fenfluramine for the treatment of Dravet syndrome patients[J]. Curr Res Pharmacol Drug Discov, 2021, 3:100078.
[73] Strzelczyk A, Pringsheim M, Mayer T, Polster T, Klotz KA, Muhle H, Alber M, Trollmann R, Spors H, Kluger G, Kurlemann G, Schubert-Bast S. Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome:compassionate use program in Germany[J]. Epilepsia, 2021, 62:2518-2527.
[74] Löscher W, Klitgaard H, Twyman RE, Schmidt D. New avenues for anti-epileptic drug discovery and development[J]. Nat Rev Drug Discov, 2013, 12:757-776.
[75] Brodie MJ. Tolerability and safety of commonly used antiepileptic drugs in adolescents and adults:a clinician's overview[J]. CNS Drugs, 2017, 31:135-147.
[76] Boada CM, French JA, Dumanis SB. Proceedings of the 15th antiepileptic drug and device trials meeting:state of the science[J]. Epilepsy Behav, 2020, 111:107189.
[77] Steriade C, French J, Devinsky O. Epilepsy:key experimental therapeutics in early clinical development[J]. Expert Opin Investig Drugs, 2020, 29:373-383.
[78] Löscher W, Sills GJ, White HS. The ups and downs of alkyl-carbamates in epilepsy therapy:how does cenobamate differ[J]? Epilepsia, 2021, 62:596-614.
[79] Auvin S. Lennox-Gastaut syndrome:new treatments and treatments under investigation[J]. Rev Neurol (Paris), 2020, 176:444-447.
[80] Bialer M, Johannessen SI, Koepp MJ, Levy RH, Perucca E, Perucca P, Tomson T, White HS. Progress report on new antiepileptic drugs:a summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT Ⅹ Ⅴ). Ⅰ:drugs in preclinical and early clinical development[J]. Epilepsia, 2020, 61:2340-2364.
[81] Bialer M, Johannessen SI, Koepp MJ, Levy RH, Perucca E, Perucca P, Tomson T, White HS. Progress report on new antiepileptic drugs:a summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT Ⅹ Ⅴ). Ⅱ:drugs in more advanced clinical development[J]. Epilepsia, 2020, 61:2365-2385.
[82] Sisodiya SM. Precision medicine and therapies of the future[J]. Epilepsia, 2021, 62 Suppl 2(Suppl 2):S90-105.
[83] Carvill GL, Dulla CG, Lowenstein DH, Brooks-Kayal AR. The path from scientific discovery to cures for epilepsy[J]. Neuropharmacology, 2020, 167:107702.
[84] Löscher W. The holy grail of epilepsy prevention:preclinical approaches to antiepileptogenic treatments[J]. Neuropharmacology, 2020, 167:107605.
[85] Schidlitzki A, Bascuñana P, Srivastava PK, Welzel L, Twele F, Töllner K, Käufer C, Gericke B, Feleke R, Meier M, Polyak A, Ross TL, Gerhauser I, Bankstahl JP, Johnson MR, Bankstahl M, Löscher W. Proof-of-concept that network pharmacology is effective to modify development of acquired temporal lobe epilepsy[J]. Neurobiol Dis, 2020, 134:104664.
[86] Welzel L, Bergin DH, Schidlitzki A, Twele F, Johne M, Klein P, Löscher W. Systematic evaluation of rationally chosen multitargeted drug combinations:a combination of low doses of levetiracetam, atorvastatin and ceftriaxone exerts antiepileptogenic effects in a mouse model of acquired epilepsy[J]. Neurobiol Dis, 2021, 149:105227.
[87] Boison D, Jarvis MF. Adenosine kinase:a key regulator of purinergic physiology[J]. Biochem Pharmacol, 2021, 187:114321.

选择文件类型/文献管理软件名称

选择包含的内容

2 癫痫药物治疗的过去、现在与未来

The past, present and future of drug therapy for epilepsy

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	薛蓉, 张轩. 睡眠障碍对脑血管病的影响[J]. 中国现代神经疾病杂志, 2023, 23(8): 659-662.
[2]	张鹏, 陈涛, 许莉. 成人失眠认知行为疗法关键技术与流程改进建议[J]. 中国现代神经疾病杂志, 2023, 23(8): 663-667.
[3]	张轩, 薛蓉. 特发性快速眼动睡眠期行为障碍向神经系统变性疾病转化的生物学标志物研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 668-673.
[4]	刘引, 汤永红, 翟锦霞, 邱媛. 慢性低度炎症与睡眠障碍研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 674-677.
[5]	于洁洋, 张亚男, 李惠敏, 黄真灿, 李宛儒, 王赞. 发作性睡病与焦虑研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 678-682.
[6]	库成心, 邓丽影, 谢亮. 缺血性卒中继发日间过度思睡研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 683-686.
[7]	姜佳凤, 赵莲花, 赵伟. 褪黑素在阿尔茨海默病病理损害机制中的作用[J]. 中国现代神经疾病杂志, 2023, 23(8): 687-692.
[8]	黄沛, 王刚. 功能性帕金森综合征诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(8): 738-741.
[9]	洪涛, 唐斌. 如何成为一名优秀的颅底外科医师[J]. 中国现代神经疾病杂志, 2023, 23(7): 571-574.
[10]	张庆硕, 宋丹丹, 周世越, 张金璐, 韩晓旭, 许顺良. 功能性步态障碍诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(7): 604-609.
[11]	潘希娟, 邢英琦, 刘玉梅. 脑小血管病影像学评分方法[J]. 中国现代神经疾病杂志, 2023, 23(7): 633-637.
[12]	俞淑凤, 李宁, 徐健, 王鹏. 颈动脉漂浮血栓相关缺血性卒中诊断与治疗进展[J]. 中国现代神经疾病杂志, 2023, 23(7): 638-642.
[13]	魏俊吉. 神经外科重症医学规范化诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(6): 477-478.
[14]	杜倩, 邓素君, 邹姗, 金珺, 周青山. 宏基因组第二代测序技术在重症中枢神经系统感染中的应用[J]. 中国现代神经疾病杂志, 2023, 23(6): 479-484.
[15]	曲鑫, 赵浩, 尚峰, 王宁. 神经重症目标温度管理[J]. 中国现代神经疾病杂志, 2023, 23(6): 485-489.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 癫痫药物治疗的过去、现在与未来

The past, present and future of drug therapy for epilepsy

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价