Research progress on the mechanism of action of perampanel and its clinical efficacy for self-limited epilepsy with centrotemporal spikes_Journal of Epilepsy

Authors：

 TANG Qi ^1,2 , TIAN Chaoyang ^1,2 , LI Ling ^1,2,3

1. Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei University for Nationalities, Enshi 445000, China;
2. Translational Medicine Center, Enshi Central Hospital, Enshi 445000 Hubei, China;
3. Key Laboratory of Hubei Province, Hubei Institute of Selenium and Human Health, Enshi 445000, China;

Corresponding author：

TANG Qi, Email: tangqi1998@126.com

Keywords：

Perampanel; Self-limited epilepsy with centrotemporal spikes; Focal epilepsy; Epileptic syndrome

DOI：

10.7507/2096-0247.202411015

Video：

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Anti-seizure medications (ASMs) are the most important and basic treatment for epilepsy, and are also the first choice for epilepsy treatment, but about one-third of patients have drug resistance. Perampanel (PER), as a novel third generation ASMs, inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) through non-competitive inhibition. AMPA plays an anti-seizure role. Since its approval in China in 2021, it has been mainly used in the treatment of focal epilepsy (with or without general seizure) as a single drug or addition, and has good safety, effectiveness and tolerability. Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a common childhood focal epilepsy syndrome, accounting for 15% ~ 25% of various childhood epilepsies, PER has important advantages in clinical studies and has shown certain curative effect. At the same time, the overall effect of PER on cognition was neutral, with no systemic cognitive deterioration or improvement. In view of the relatively short application time of PER, which is still a new drug, this article will review the mechanism of action, dose, add-on (single drug) treatment, adverse events and, in order to provide clinicians with more drug choices and facilitate the individualized diagnosis and treatment of epilepsy.

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5.	Potschka H, Trinka E. Perampanel: does it have broad-spectrum potential? Epilepsia, 2019, 60(Suppl 1): 22-36.
6.	Moresco L, Bruschettini M, Calevo MG, et al. Pharmacological treatment for continuous spike-wave during slow wave sleep syndrome and Landau-Kleffner syndrome. Cochrane Database Syst Rev, 2020, 11(11): CD013132.
7.	Jellinek ER, Duda TA, Fein RH. The RUBI parent training for disruptive behavior in a child with electrical status epilepticus in sleep (ESES): a case report. J Clin Psychol Med Settings, 2023, 30(4): 770-779.
8.	Zhang Y, Gao B, Zheng F, et al. The phosphodiesterase 10A Inhibitor PF-2545920 enhances hippocampal excitability and seizure activity involving the upregulation of GluA1 and NR2A in post-synaptic densities. Front Mol Neurosci, 2017, 10: 100.
9.	Meldrum BS, Akbar MT, Chapman AG. Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res, 1999, 36(2-3): 189-204.
10.	易珈沁, 孙丹. 吡仑帕奈治疗局灶性癫痫的研究进展. 国际神经病学神经外科学杂志, 2023, 50(4): 85-89.
11.	Yelshanskaya MV, Singh AK, Sampson JM, et al. Structural bases of noncompetitive inhibition of AMPA-subtype ionotropic glutamate receptors by antiepileptic drugs. Neuron, 2016, 91(6): 1305-1315.
12.	Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit, 2018, 40(5): 526-548.
13.	Yamamoto Y, Usui N, Nishida T, et al. Therapeutic drug monitoring for perampanel in Japanese epilepsy patients: influence of concomitant antiepileptic drugs. Ther Drug Monit, 2017, 39(4): 446-449.
14.	《药学与临床研究》编辑部编译. 2014年美国上市新药选编. 药学与临床研究, 2015, 23(1): 87-96.
15.	De Liso P, Moavero R, Coppola G, et al. Current role of perampanel in pediatric epilepsy. Ital J Pediatr, 2017, 43(1): 51.
16.	Villanueva V, Garcés M, López-González FJ, et al. Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: the FYDATA study. Epilepsy Res, 2016, 126: 201-210.
17.	Brodie MJ, Stephen LJ. Prospective audit with adjunctive perampanel: preliminary observations in focal epilepsy. Epilepsy Behav, 2016, 54: 100-103.
18.	Yamamoto Y, Shiratani Y, Asai S, et al. Risk factors for psychiatric adverse effects associated with perampanel therapy. Epilepsy Behav, 2021, 10: 1521.
19.	Heyman E, Lahat E, Levin N, et al. Tolerability and efficacy of perampanel in children with refractory epilepsy. Dev Med Child Neurol, 2017, 59(4): 441-444.
20.	Tsai JJ, Wu T, Leung H, et al. Perampanel, an AMPA receptor antagonist: from clinical research to practice in clinical settings. Acta Neurol Scand, 2018, 137(4): 378-391.
21.	Takenaka O, Ferry J, Saeki K, et al. Pharmacokinetic/pharmacodynamic analysis of adjunctive perampanel in subjects with partial-onset seizures. Acta Neurol Scand, 2018, 137(4): 400-408.
22.	褚思嘉, 汤继宏. 第三代新型抗癫痫药吡仑帕奈在癫痫治疗中的研究进展. 癫痫杂志, 2021, 7(1): 58-61.
23.	Kanner AM, Bicchi MM. Review of antiseizure medications for adults with epilepsy-reply. JAMA, 2022, 328(7): 681.
24.	Öztoprak Ü, Yayici Köken Ö, Aksoy E, et al. Spike-wave index assessment and electro-clinical correlation in patients with encephalopathy associated with epileptic state during slow sleep (ESES/CSWS), single-center experience. Epilepsy Res, 2021, 170: 106549.
25.	马湖萍. 新型抗癫痫发作药物吡仑帕奈添加治疗0~18岁儿童难治性癫痫的临床观察研究. 中国全科医学, 2025, 28(2): 250-256.
26.	岳璇. 吡仑帕奈单药治疗伴中央颞区棘波的自限性癫痫疗效观察及安全性研究. 癫痫杂志, 2023, 9(5): 388-392.
27.	Ma H, Zhu H, Chen F, et al. Efficacy and safety of perampanel monotherapy in Chinese patients with focal-onset seizures: a single-center, prospective, real-world observational study. Epilepsia Open, 2023, 8(4): 1474-1483.
28.	Biró A, Stephani U, Tarallo T, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies: first experiences. Neuropediatrics, 2015, 46(2): 110-116.
29.	de Liso P, Vigevano F, Specchio N, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study. EpilepsyRes, 2016, 127: 93-100.
30.	Meador KJ, Yang H, Piña-Garza JE, et al. Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial. Epilepsia, 2016, 57(2): 243-251.
31.	Enserink JM. Sumo during stress: when transcription takes a pause. Bioessays, 2017, 39(6): 125-127.
32.	雒晨宇, 孙美珍. 吡仑帕奈单药治疗对癫痫患者睡眠及认知的影响. 实用药物与临床, 2023, 26(11): 990-994.

1. Löscher W, Potschka H, Sisodiya SM, et al. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev, 2020, 72(3): 606-638.
2. Lattanzi S, Striano P. The impact of perampanel and targeting AMPA transmission on anti-seizure drug discovery. Expert Opin Drug Discov, 2019, 14(3): 195-197.
3. 经力. 吡仑帕奈治疗儿童癫痫的病例报道及文献阅读. 实用药物与临床, 2022, 25(5): 417-420.
4. Chinvarun Y, Huang CW, Wu Y, et al. Optimal use of perampanel in asian patients with epilepsy: expert opinion. Ther Clin Risk Manag, 2021, 17: 739-746.
5. Potschka H, Trinka E. Perampanel: does it have broad-spectrum potential? Epilepsia, 2019, 60(Suppl 1): 22-36.
6. Moresco L, Bruschettini M, Calevo MG, et al. Pharmacological treatment for continuous spike-wave during slow wave sleep syndrome and Landau-Kleffner syndrome. Cochrane Database Syst Rev, 2020, 11(11): CD013132.
7. Jellinek ER, Duda TA, Fein RH. The RUBI parent training for disruptive behavior in a child with electrical status epilepticus in sleep (ESES): a case report. J Clin Psychol Med Settings, 2023, 30(4): 770-779.
8. Zhang Y, Gao B, Zheng F, et al. The phosphodiesterase 10A Inhibitor PF-2545920 enhances hippocampal excitability and seizure activity involving the upregulation of GluA1 and NR2A in post-synaptic densities. Front Mol Neurosci, 2017, 10: 100.
9. Meldrum BS, Akbar MT, Chapman AG. Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res, 1999, 36(2-3): 189-204.
10. 易珈沁, 孙丹. 吡仑帕奈治疗局灶性癫痫的研究进展. 国际神经病学神经外科学杂志, 2023, 50(4): 85-89.
11. Yelshanskaya MV, Singh AK, Sampson JM, et al. Structural bases of noncompetitive inhibition of AMPA-subtype ionotropic glutamate receptors by antiepileptic drugs. Neuron, 2016, 91(6): 1305-1315.
12. Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit, 2018, 40(5): 526-548.
13. Yamamoto Y, Usui N, Nishida T, et al. Therapeutic drug monitoring for perampanel in Japanese epilepsy patients: influence of concomitant antiepileptic drugs. Ther Drug Monit, 2017, 39(4): 446-449.
14. 《药学与临床研究》编辑部编译. 2014年美国上市新药选编. 药学与临床研究, 2015, 23(1): 87-96.
15. De Liso P, Moavero R, Coppola G, et al. Current role of perampanel in pediatric epilepsy. Ital J Pediatr, 2017, 43(1): 51.
16. Villanueva V, Garcés M, López-González FJ, et al. Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: the FYDATA study. Epilepsy Res, 2016, 126: 201-210.
17. Brodie MJ, Stephen LJ. Prospective audit with adjunctive perampanel: preliminary observations in focal epilepsy. Epilepsy Behav, 2016, 54: 100-103.
18. Yamamoto Y, Shiratani Y, Asai S, et al. Risk factors for psychiatric adverse effects associated with perampanel therapy. Epilepsy Behav, 2021, 10: 1521.
19. Heyman E, Lahat E, Levin N, et al. Tolerability and efficacy of perampanel in children with refractory epilepsy. Dev Med Child Neurol, 2017, 59(4): 441-444.
20. Tsai JJ, Wu T, Leung H, et al. Perampanel, an AMPA receptor antagonist: from clinical research to practice in clinical settings. Acta Neurol Scand, 2018, 137(4): 378-391.
21. Takenaka O, Ferry J, Saeki K, et al. Pharmacokinetic/pharmacodynamic analysis of adjunctive perampanel in subjects with partial-onset seizures. Acta Neurol Scand, 2018, 137(4): 400-408.
22. 褚思嘉, 汤继宏. 第三代新型抗癫痫药吡仑帕奈在癫痫治疗中的研究进展. 癫痫杂志, 2021, 7(1): 58-61.
23. Kanner AM, Bicchi MM. Review of antiseizure medications for adults with epilepsy-reply. JAMA, 2022, 328(7): 681.
24. Öztoprak Ü, Yayici Köken Ö, Aksoy E, et al. Spike-wave index assessment and electro-clinical correlation in patients with encephalopathy associated with epileptic state during slow sleep (ESES/CSWS), single-center experience. Epilepsy Res, 2021, 170: 106549.
25. 马湖萍. 新型抗癫痫发作药物吡仑帕奈添加治疗0~18岁儿童难治性癫痫的临床观察研究. 中国全科医学, 2025, 28(2): 250-256.
26. 岳璇. 吡仑帕奈单药治疗伴中央颞区棘波的自限性癫痫疗效观察及安全性研究. 癫痫杂志, 2023, 9(5): 388-392.
27. Ma H, Zhu H, Chen F, et al. Efficacy and safety of perampanel monotherapy in Chinese patients with focal-onset seizures: a single-center, prospective, real-world observational study. Epilepsia Open, 2023, 8(4): 1474-1483.
28. Biró A, Stephani U, Tarallo T, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies: first experiences. Neuropediatrics, 2015, 46(2): 110-116.
29. de Liso P, Vigevano F, Specchio N, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study. EpilepsyRes, 2016, 127: 93-100.
30. Meador KJ, Yang H, Piña-Garza JE, et al. Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial. Epilepsia, 2016, 57(2): 243-251.
31. Enserink JM. Sumo during stress: when transcription takes a pause. Bioessays, 2017, 39(6): 125-127.
32. 雒晨宇, 孙美珍. 吡仑帕奈单药治疗对癫痫患者睡眠及认知的影响. 实用药物与临床, 2023, 26(11): 990-994.

Journal of Epilepsy

Latest ArticlesResearch progress on the mechanism of action of perampanel and its clinical efficacy for self-limited epilepsy with centrotemporal spikes

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