Research progress of clinical application of perampanel_Journal of Epilepsy

Authors：

ZHANG Kaiyue , ZHENG Zhaoshi , WANG Han ,  LIU Songyan

Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130033, China;

Corresponding author：

LIU Songyan, Email: liu_sy@jlu.edu.cn

Keywords：

Perampanel; Epilepsy; Anti-seizure medications; Clinical research

DOI：

10.7507/2096-0247.202303008

Video：

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Abstract Full text Figures/Tables Video References Cited by

Epilepsy is a common chronic disease of the nervous system, which has certain adverse effects on the cognitive, psychological and social functions of the patients. To date, anti-seizure medications (ASMs) remain the first-line treatment option for epilepsy, but many patients with epilepsy still do not have effective seizure control when multiple ASMs are used in combination. Therefore, there is an urgent need for a new target and mechanism ASMs to bring about new treatment options and hope for patients with intractable epilepsy. Perampanel, a new third-generation ASMs, whereas second-generation ASMs tend to exert anti-seizure effects mainly by regulating ion channels or enhancing related mechanisms such as gamma-aminobutyric acid (GABA) effects, perampanel exerts its effects mainly by targeting the excitatory neurotransmitter glutamate. Perampanel is the first selective α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist and the first selective inhibitory ASMs for excitatory postsynaptic function. Because of its unique target and mechanism, it has been approved by many countries in the world for adjuvant additive therapy and monotherapy for patients with focal and general epilepsy. In addition, with the discovery of the neuroprotective, antioxidant, neurotransmitter regulation effects of perampanel, it also provides a new potential choice for the treatment of other diseases. This article mainly reviews the mechanism of action, pharmacokinetics, clinical trials and treatment of other diseases other than epilepsy of perampanel.

Citation： ZHANG Kaiyue, ZHENG Zhaoshi, WANG Han, LIU Songyan. Research progress of clinical application of perampanel. Journal of Epilepsy, 2023, 9(3): 210-217. doi: 10.7507/2096-0247.202303008 Copy

1.	Vezzani A, Ravizza T, Bedner P, et al. Astrocytes in the initiation and progression of epilepsy. Nat Rev Neurol, 2022, 18(12): 707-722.
2.	Keller BU, Hollmann M, Heinemann S, et al. Calcium influx through subunits GluR1/GluR3 of kainate/AMPA receptor channels is regulated by cAMP dependent protein kinase. EMBO J, 1992, 11(3): 891-896.
3.	Hanley JG. Subunit-specific trafficking mechanisms regulating the synaptic expression of Ca(2+)-permeable AMPA receptors. Semin Cell Dev Biol, 2014, 27: 14-22.
4.	Isaac JTR, Ashby MC, McBain CJ. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron, 2007, 54(6): 859-871.
5.	Barygin OI. Inhibition of calcium-permeable and calcium-impermeable AMPA receptors by perampanel in rat brain neurons. Neurosci Lett, 2016, 633: 146-151.
6.	史卫忠, 徐春敏, 韩容. 新型口服抗癫痫药吡仑帕奈. 药品评价, 2012, 9(29): 33-37.
7.	Faulkner MA. Perampanel: a new agent for adjunctive treatment of partial seizures. Am J Health Syst Pharm, 2014, 71(3): 191-198.
8.	Chen T, Dai S, Jiang Z, et al. The AMPAR antagonist perampanel attenuates traumatic brain injury through anti-oxidative and anti-inflammatory activity. Cell Mol Neurobiol, 2017, 37(1): 43-52.
9.	Chen T, Yang L, Zhu J, et al. The AMPAR antagonist perampanel regulates neuronal necroptosis via Akt/GSK3β signaling after acute traumatic injury in cortical neuron. CNS Neurol Disord Drug Targets, 2021, 20(3): 266-272.
10.	Chen T, Liu W, Qian X, et al. The AMPAR antagonist perampanel protects the neurovascular unit against traumatic injury via regulating Sirt3. CNS Neuroscience & Therapeutics, 2021, 27(1): 134-144.
11.	Kawakita F, Kanamaru H, Asada R, et al. Inhibition of AMPA (alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate) receptor reduces acute blood-brain barrier disruption after subarachnoid hemorrhage in mice. Transl Stroke Res, 2022, 13(2): 326-337.
12.	Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl, 2013, (197): 19-24.
13.	Laurenza A, Yang H, Williams B, et al. Absence of liver toxicity in perampanel-treated subjects: pooled results from partial seizure phase III perampanel clinical studies. Epilepsy Res, 2015, 113: 76-85.
14.	Krauss GL, Serratosa JM, Villanueva V, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology, 2012, 78(18): 1408-1415.
15.	Patsalos PN, Gougoulaki M, Sander JW. Perampanel serum concentrations in adults with epilepsy: effect of dose, age, sex, and concomitant anti-epileptic drugs. Ther Drug Monit, 2016, 38(3): 358-364.
16.	Vazquez B, Tomson T, Dobrinsky C, et al. Perampanel and pregnancy. Epilepsia, 2021, 62(3): 698-708.
17.	Renfroe JB, Mintz M, Davis R, et al. Adjunctive perampanel oral suspension in pediatric patients from ≥2 to <12 years of age with epilepsy: pharmacokinetics, safety, tolerability, and efficacy. J Child Neurol, 2019, 34(5): 284-294.
18.	Inoue Y, Sumitomo K, Matsutani K, et al. Evaluation of real-world effectiveness of perampanel in Japanese adults and older adults with epilepsy. Epileptic Disord, 2022, 24(1): 123-132.
19.	Lattanzi S, Cagnetti C, Foschi N, et al. Adjunctive perampanel in older patients with epilepsy: a multicenter study of clinical practice. Drugs Aging, 2021, 38(7): 603-610.
20.	Krauss GL, Bar M, Biton V, et al. Tolerability and safety of perampanel: two randomized dose-escalation studies. Acta Neurol Scand, 2012, 125(1): 8-15.
21.	French JA, Krauss GL, Biton V, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology, 2012, 79(6): 589-596.
22.	French JA, Krauss GL, Steinhoff BJ, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia, 2013, 54(1): 117-125.
23.	Nishida T, Lee SK, Inoue Y, et al. Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study. Acta Neurol Scand, 2018, 137(4): 392-399.
24.	Krauss GL, Perucca E, Ben-Menachem E, et al. Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307. Epilepsia, 2014, 55(7): 1058-1068.
25.	French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy: a randomized trial. Neurology, 2015, 85(11): 950-957.
26.	French JA, Wechsler RT, Trinka E, et al. Long-term open-label perampanel: generalized tonic-clonic seizures in idiopathic generalized epilepsy. Epilepsia Open, 2022, 7(3): 393-405.
27.	Brandt C, Wechsler RT, O'Brien TJ, et al. Adjunctive perampanel and myoclonic and absence seizures: post hoc analysis of data from study 332 in patients with idiopathic generalized epilepsy. Seizure, 2020, 80: 115-123.
28.	Villanueva V, Montoya J, Castillo A, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study. Epilepsia, 2018, 59(9): 1740-1752.
29.	Trinka E, Lattanzi S, Carpenter K, et al. Exploring the evidence for broad-spectrum effectiveness of perampanel: a systematic review of clinical data in generalised seizures. CNS Drugs, 2021, 35(8): 821-837.
30.	Santamarina E, Bertol V, Garayoa V, et al. Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs. Seizure, 2020, 83: 48-56.
31.	Kim JH, Kim DW, Lee SK, et al. First add-on perampanel for focal-onset seizures: an open-label, prospective study. Acta Neurol Scand, 2020, 141(2): 132-140.
32.	Takahashi S, Shimizu K, Inaji M, et al. Effectiveness of perampanel as a first add-on antiepileptic drug for the treatment of partial epilepsy. Epilepsy & Behavior, 2019, 100（Pt A）: 106492.
33.	Yamamoto T, Lim SC, Ninomiya H, et al. Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: the open-label Study 342 (FREEDOM Study). Epilepsia Open, 2020, 5(2): 274-284.
34.	Hanada T, Ido K, Kosasa T. Effect of perampanel, a novel AMPA antagonist, on benzodiazepine-resistant status epilepticus in a lithium-pilocarpine rat model. Pharmacol Res Perspect, 2014, 2(5): e00063.
35.	Wu T, Ido K, Osada Y, et al. The neuroprotective effect of perampanel in lithium-pilocarpine rat seizure model. Epilepsy Res, 2017, 137: 152-158.
36.	Mohammad H, Sekar S, Wei Z, et al. Perampanel but not amantadine prevents behavioral alterations and epileptogenesis in pilocarpine rat model of status epilepticus. Mol Neurobiol, 2019, 56(4): 2508-2523.
37.	Lim SN, Wu T, Tseng WJ, et al. Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review. J Neurol, 2021, 268(10): 3744-3757.
38.	Ho CJ, Lin CH, Lu YT, et al. Perampanel treatment for refractory status epilepticus in a neurological intensive care unit. Neurocrit Care, 2019, 31(1): 24-29.
39.	Alsherbini K, Abhi Pandhi F, Goyanes J, et al. A retrospective, observational study of perampanel in refractory and super-refractory status epilepticus. J Neurol Sci, 2020, 419: 117214.
40.	Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
41.	Crespel A, Tang NPL, Macorig G, et al. Open-label, uncontrolled retrospective study of perampanel in adults with Lennox-Gastaut syndrome. Seizure, 2020, 75: 66-69.
42.	Auvin S, Dozieres B, Ilea A, et al. Use of perampanel in children and adolescents with Lennox-Gastaut Syndrome. Epilepsy Behav, 2017, 74: 59-63.
43.	Ho S, Lin L, Chen IC, et al. Perampanel reduces hyperthermia-induced seizures in dravet syndrome mouse model. Front Pharmacol, 2021, 12: 682767.
44.	Yoshitomi S, Takahashi Y, Yamaguchi T, et al. Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome. Epilepsy Res, 2019, 154: 34-38.
45.	Nozawa A, Ozeki M, Matsuoka M, et al. Perampanel inhibits neuroblastoma cell proliferation through down-regulation of AKT and ERK pathways. Anticancer Res, 2019, 39(7): 3595-3599.
46.	Lange F, Wesslau K, Porath K, et al. AMPA receptor antagonist perampanel affects glioblastoma cell growth and glutamate release in vitro. PLoS One, 2019, 14(2): e0211644.
47.	Obara K, Abe E, Toyoshima I. Frontal Hypoperfusion and the Effectiveness of Perampanel in Long-Lived Patient with Lafora Disease. Case Rep Neurol, 2021, 13(1): 211-217.
48.	Schorlemmer K, Bauer S, Belke M, et al. Sustained seizure remission on perampanel in progressive myoclonic epilepsy (Lafora disease). Epilepsy Behav, 2013, 1: 118-121.
49.	Goldsmith D, Minassian BA. Efficacy and tolerability of perampanel in ten patients with Lafora disease. Epilepsy Behav, 2016, 62: 132-135.
50.	Ortolano S, Vieitez I, Agis-Balboa RC, et al. Loss of GABAergic cortical neurons underlies the neuropathology of Lafora disease. Mol Brain, 2014, 7: 7.
51.	Dirani M, Nasreddine W, Abdulla F, et al. Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel. Epilepsy & Behavior Case Reports, 2014, 2: 164-166.
52.	Assenza G, Nocerino C, Tombini M, et al. Perampanel improves cortical myoclonus and disability in progressive myoclonic epilepsies: a case series and a systematic review of the literature. Front Neurol, 2021, 12: 630366.
53.	Marin C, Jiménez A, Bonastre M, et al. LY293558, an AMPA glutamate receptor antagonist, prevents and reverses levodopa-induced motor alterations in Parkinsonian rats. Synapse, 2001, 42(1): 40-47.
54.	Klockgether T, Turski L, Honoré T, et al. The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys. Ann Neurol, 1991, 30(5): 717-723.
55.	Konitsiotis S, Blanchet PJ, Verhagen L, et al. AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology, 2000, 54(8): 1589-1595.
56.	Ueda J, Uemura N, Sawamura M, et al. Perampanel inhibits α-synuclein transmission in parkinson's disease models. Mov Disord, 2021, 36(7): 1554-1564.
57.	Eggert K, Squillacote D, Barone P, et al. Safety and efficacy of perampanel in advanced Parkinson's disease: a randomized, placebo-controlled study. Mov Disord, 2010, 25(7): 896-905.
58.	Lees A, Fahn S, Eggert KM, et al. Perampanel, an AMPA antagonist, found to have no benefit in reducing "off" time in Parkinson's disease. Mov Disord, 2012, 27(2): 284-288.
59.	Akamatsu M, Yamashita T, Hirose N, et al. The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice. Sci Rep, 2016, 6: 28649.
60.	Aizawa H, Kato H, Oba K, et al. Randomized phase 2 study of perampanel for sporadic amyotrophic lateral sclerosis. Journal of Neurology, 2022, 269(2): 885-896.
61.	Turalde CWR, Moalong KMC, Espiritu AI, et al. Perampanel for amyotrophic lateral sclerosis: a systematic review and meta-analysis. Neurol Sci, 2022, 43(2): 889-897.
62.	Garcia D, Cano I. New concepts in the management of restless legs syndrome. BMJ, 2017, 356: j104.
63.	Garcia D, Cano I, Granizo J. Treatment of restless legs syndrome with the selective AMPA receptor antagonist perampanel. Sleep Med, 2017, 34: 105-108.

1. Vezzani A, Ravizza T, Bedner P, et al. Astrocytes in the initiation and progression of epilepsy. Nat Rev Neurol, 2022, 18(12): 707-722.
2. Keller BU, Hollmann M, Heinemann S, et al. Calcium influx through subunits GluR1/GluR3 of kainate/AMPA receptor channels is regulated by cAMP dependent protein kinase. EMBO J, 1992, 11(3): 891-896.
3. Hanley JG. Subunit-specific trafficking mechanisms regulating the synaptic expression of Ca(2+)-permeable AMPA receptors. Semin Cell Dev Biol, 2014, 27: 14-22.
4. Isaac JTR, Ashby MC, McBain CJ. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron, 2007, 54(6): 859-871.
5. Barygin OI. Inhibition of calcium-permeable and calcium-impermeable AMPA receptors by perampanel in rat brain neurons. Neurosci Lett, 2016, 633: 146-151.
6. 史卫忠, 徐春敏, 韩容. 新型口服抗癫痫药吡仑帕奈. 药品评价, 2012, 9(29): 33-37.
7. Faulkner MA. Perampanel: a new agent for adjunctive treatment of partial seizures. Am J Health Syst Pharm, 2014, 71(3): 191-198.
8. Chen T, Dai S, Jiang Z, et al. The AMPAR antagonist perampanel attenuates traumatic brain injury through anti-oxidative and anti-inflammatory activity. Cell Mol Neurobiol, 2017, 37(1): 43-52.
9. Chen T, Yang L, Zhu J, et al. The AMPAR antagonist perampanel regulates neuronal necroptosis via Akt/GSK3β signaling after acute traumatic injury in cortical neuron. CNS Neurol Disord Drug Targets, 2021, 20(3): 266-272.
10. Chen T, Liu W, Qian X, et al. The AMPAR antagonist perampanel protects the neurovascular unit against traumatic injury via regulating Sirt3. CNS Neuroscience & Therapeutics, 2021, 27(1): 134-144.
11. Kawakita F, Kanamaru H, Asada R, et al. Inhibition of AMPA (alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate) receptor reduces acute blood-brain barrier disruption after subarachnoid hemorrhage in mice. Transl Stroke Res, 2022, 13(2): 326-337.
12. Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl, 2013, (197): 19-24.
13. Laurenza A, Yang H, Williams B, et al. Absence of liver toxicity in perampanel-treated subjects: pooled results from partial seizure phase III perampanel clinical studies. Epilepsy Res, 2015, 113: 76-85.
14. Krauss GL, Serratosa JM, Villanueva V, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology, 2012, 78(18): 1408-1415.
15. Patsalos PN, Gougoulaki M, Sander JW. Perampanel serum concentrations in adults with epilepsy: effect of dose, age, sex, and concomitant anti-epileptic drugs. Ther Drug Monit, 2016, 38(3): 358-364.
16. Vazquez B, Tomson T, Dobrinsky C, et al. Perampanel and pregnancy. Epilepsia, 2021, 62(3): 698-708.
17. Renfroe JB, Mintz M, Davis R, et al. Adjunctive perampanel oral suspension in pediatric patients from ≥2 to <12 years of age with epilepsy: pharmacokinetics, safety, tolerability, and efficacy. J Child Neurol, 2019, 34(5): 284-294.
18. Inoue Y, Sumitomo K, Matsutani K, et al. Evaluation of real-world effectiveness of perampanel in Japanese adults and older adults with epilepsy. Epileptic Disord, 2022, 24(1): 123-132.
19. Lattanzi S, Cagnetti C, Foschi N, et al. Adjunctive perampanel in older patients with epilepsy: a multicenter study of clinical practice. Drugs Aging, 2021, 38(7): 603-610.
20. Krauss GL, Bar M, Biton V, et al. Tolerability and safety of perampanel: two randomized dose-escalation studies. Acta Neurol Scand, 2012, 125(1): 8-15.
21. French JA, Krauss GL, Biton V, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology, 2012, 79(6): 589-596.
22. French JA, Krauss GL, Steinhoff BJ, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia, 2013, 54(1): 117-125.
23. Nishida T, Lee SK, Inoue Y, et al. Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study. Acta Neurol Scand, 2018, 137(4): 392-399.
24. Krauss GL, Perucca E, Ben-Menachem E, et al. Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307. Epilepsia, 2014, 55(7): 1058-1068.
25. French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy: a randomized trial. Neurology, 2015, 85(11): 950-957.
26. French JA, Wechsler RT, Trinka E, et al. Long-term open-label perampanel: generalized tonic-clonic seizures in idiopathic generalized epilepsy. Epilepsia Open, 2022, 7(3): 393-405.
27. Brandt C, Wechsler RT, O'Brien TJ, et al. Adjunctive perampanel and myoclonic and absence seizures: post hoc analysis of data from study 332 in patients with idiopathic generalized epilepsy. Seizure, 2020, 80: 115-123.
28. Villanueva V, Montoya J, Castillo A, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study. Epilepsia, 2018, 59(9): 1740-1752.
29. Trinka E, Lattanzi S, Carpenter K, et al. Exploring the evidence for broad-spectrum effectiveness of perampanel: a systematic review of clinical data in generalised seizures. CNS Drugs, 2021, 35(8): 821-837.
30. Santamarina E, Bertol V, Garayoa V, et al. Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs. Seizure, 2020, 83: 48-56.
31. Kim JH, Kim DW, Lee SK, et al. First add-on perampanel for focal-onset seizures: an open-label, prospective study. Acta Neurol Scand, 2020, 141(2): 132-140.
32. Takahashi S, Shimizu K, Inaji M, et al. Effectiveness of perampanel as a first add-on antiepileptic drug for the treatment of partial epilepsy. Epilepsy & Behavior, 2019, 100（Pt A）: 106492.
33. Yamamoto T, Lim SC, Ninomiya H, et al. Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: the open-label Study 342 (FREEDOM Study). Epilepsia Open, 2020, 5(2): 274-284.
34. Hanada T, Ido K, Kosasa T. Effect of perampanel, a novel AMPA antagonist, on benzodiazepine-resistant status epilepticus in a lithium-pilocarpine rat model. Pharmacol Res Perspect, 2014, 2(5): e00063.
35. Wu T, Ido K, Osada Y, et al. The neuroprotective effect of perampanel in lithium-pilocarpine rat seizure model. Epilepsy Res, 2017, 137: 152-158.
36. Mohammad H, Sekar S, Wei Z, et al. Perampanel but not amantadine prevents behavioral alterations and epileptogenesis in pilocarpine rat model of status epilepticus. Mol Neurobiol, 2019, 56(4): 2508-2523.
37. Lim SN, Wu T, Tseng WJ, et al. Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review. J Neurol, 2021, 268(10): 3744-3757.
38. Ho CJ, Lin CH, Lu YT, et al. Perampanel treatment for refractory status epilepticus in a neurological intensive care unit. Neurocrit Care, 2019, 31(1): 24-29.
39. Alsherbini K, Abhi Pandhi F, Goyanes J, et al. A retrospective, observational study of perampanel in refractory and super-refractory status epilepticus. J Neurol Sci, 2020, 419: 117214.
40. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
41. Crespel A, Tang NPL, Macorig G, et al. Open-label, uncontrolled retrospective study of perampanel in adults with Lennox-Gastaut syndrome. Seizure, 2020, 75: 66-69.
42. Auvin S, Dozieres B, Ilea A, et al. Use of perampanel in children and adolescents with Lennox-Gastaut Syndrome. Epilepsy Behav, 2017, 74: 59-63.
43. Ho S, Lin L, Chen IC, et al. Perampanel reduces hyperthermia-induced seizures in dravet syndrome mouse model. Front Pharmacol, 2021, 12: 682767.
44. Yoshitomi S, Takahashi Y, Yamaguchi T, et al. Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome. Epilepsy Res, 2019, 154: 34-38.
45. Nozawa A, Ozeki M, Matsuoka M, et al. Perampanel inhibits neuroblastoma cell proliferation through down-regulation of AKT and ERK pathways. Anticancer Res, 2019, 39(7): 3595-3599.
46. Lange F, Wesslau K, Porath K, et al. AMPA receptor antagonist perampanel affects glioblastoma cell growth and glutamate release in vitro. PLoS One, 2019, 14(2): e0211644.
47. Obara K, Abe E, Toyoshima I. Frontal Hypoperfusion and the Effectiveness of Perampanel in Long-Lived Patient with Lafora Disease. Case Rep Neurol, 2021, 13(1): 211-217.
48. Schorlemmer K, Bauer S, Belke M, et al. Sustained seizure remission on perampanel in progressive myoclonic epilepsy (Lafora disease). Epilepsy Behav, 2013, 1: 118-121.
49. Goldsmith D, Minassian BA. Efficacy and tolerability of perampanel in ten patients with Lafora disease. Epilepsy Behav, 2016, 62: 132-135.
50. Ortolano S, Vieitez I, Agis-Balboa RC, et al. Loss of GABAergic cortical neurons underlies the neuropathology of Lafora disease. Mol Brain, 2014, 7: 7.
51. Dirani M, Nasreddine W, Abdulla F, et al. Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel. Epilepsy & Behavior Case Reports, 2014, 2: 164-166.
52. Assenza G, Nocerino C, Tombini M, et al. Perampanel improves cortical myoclonus and disability in progressive myoclonic epilepsies: a case series and a systematic review of the literature. Front Neurol, 2021, 12: 630366.
53. Marin C, Jiménez A, Bonastre M, et al. LY293558, an AMPA glutamate receptor antagonist, prevents and reverses levodopa-induced motor alterations in Parkinsonian rats. Synapse, 2001, 42(1): 40-47.
54. Klockgether T, Turski L, Honoré T, et al. The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys. Ann Neurol, 1991, 30(5): 717-723.
55. Konitsiotis S, Blanchet PJ, Verhagen L, et al. AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology, 2000, 54(8): 1589-1595.
56. Ueda J, Uemura N, Sawamura M, et al. Perampanel inhibits α-synuclein transmission in parkinson's disease models. Mov Disord, 2021, 36(7): 1554-1564.
57. Eggert K, Squillacote D, Barone P, et al. Safety and efficacy of perampanel in advanced Parkinson's disease: a randomized, placebo-controlled study. Mov Disord, 2010, 25(7): 896-905.
58. Lees A, Fahn S, Eggert KM, et al. Perampanel, an AMPA antagonist, found to have no benefit in reducing "off" time in Parkinson's disease. Mov Disord, 2012, 27(2): 284-288.
59. Akamatsu M, Yamashita T, Hirose N, et al. The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice. Sci Rep, 2016, 6: 28649.
60. Aizawa H, Kato H, Oba K, et al. Randomized phase 2 study of perampanel for sporadic amyotrophic lateral sclerosis. Journal of Neurology, 2022, 269(2): 885-896.
61. Turalde CWR, Moalong KMC, Espiritu AI, et al. Perampanel for amyotrophic lateral sclerosis: a systematic review and meta-analysis. Neurol Sci, 2022, 43(2): 889-897.
62. Garcia D, Cano I. New concepts in the management of restless legs syndrome. BMJ, 2017, 356: j104.
63. Garcia D, Cano I, Granizo J. Treatment of restless legs syndrome with the selective AMPA receptor antagonist perampanel. Sleep Med, 2017, 34: 105-108.

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