Klein P, Friedman D, Kwan P. Recent advances in pharmacologic treatments of drug-resistant epilepsy: breakthrough in sight. CNS Drugs. 2024;38(12):949–60.

Article  PubMed  Google Scholar 

Melnick SM, Misra SN, Kamin M, Ferrari L, Glenn KJ. Potential of cenobamate as a broad-spectrum antiseizure medication. Expert Opin Pharmacother. 2025;26(10):1177–89.

Article  CAS  PubMed  Google Scholar 

Krauss GL, Klein P, Brandt C, Lee SK, Milanov I, Milovanovic M, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020;19:38–48.

Article  CAS  PubMed  Google Scholar 

Chung SS, French JA, Kowalski J, Krauss GL, Lee SK, Maciejowski M, et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020;94(22):e2311–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Klein P, Aboumatar S, Brandt C, Dong F, Krauss GL, Mizne S, et al. Long-term efficacy and safety from an open-label extension of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2022;99(10):e989–98.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sperling MR, Klein P, Aboumatar S, Gelfand M, Halford JJ, Krauss GL, et al. Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open-label safety study. Epilepsia. 2020;61(6):1099–108.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abou-Khalil B, Aboumatar S, Klein P, Krauss GL, Sperling MR, Rosenfeld WE. Efficacy of cenobamate for uncontrolled focal seizures in patients with previous epilepsy-related surgery: post hoc analysis of a phase 3, multicenter, open-label study. Epilepsy Res. 2022;184:106952.

Article  CAS  PubMed  Google Scholar 

Toledo M, Abraira L, López-Maza S, Boy B, Campos-Fernández D, Quintana M, et al. Steps towards seizure freedom with the use of cenobamate. Epilepsy Behav. 2025;170:110464.

Article  CAS  PubMed  Google Scholar 

Gjerulfsen CE, Juhl S, Mieszczanek KM, Spanil L, Thygesen KS, Pavbro A, et al. Cenobamate as add-on treatment in ultra-refractory focal epilepsy: real-world results from the Danish Epilepsy Centre, Dianalund, Denmark. Neurol Sci. 2025;46(8):3875–84.

Article  PubMed  PubMed Central  Google Scholar 

Zengin E, Erol F, Gil GA, Lado FA. Cenobamate monotherapy for focal epilepsy: a single-center retrospective study. Neurol Clin Pract. 2025;15(3):e200460.

Article  PubMed  PubMed Central  Google Scholar 

Rheims S, Steinhoff BJ, Hirsch E, Rosenow F, Biraben A, Thomas R, et al. Real-world effectiveness and tolerability of cenobamate in drug-resistant epilepsy: a retrospective analysis of the patients included into the early access programs (EAP) in Germany, France, and United Kingdom. Epilepsia Open. 2025;10(3):736–48.

Article  PubMed  PubMed Central  Google Scholar 

Specchio N, Pietrafusa N, Vigevano F. Is cenobamate the breakthrough we have been wishing for? Int J Mol Sci. 2021;22(17):9339.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia. 2011;52(4):657–78.

Article  PubMed  Google Scholar 

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. JAMA Neurol. 2018;75(3):279–86.

Article  PubMed  PubMed Central  Google Scholar 

French JA. Do you believe in magic (bullets)? Epilepsy Curr. 2020;20(6 Suppl.):24S-S26.

Article  PubMed  PubMed Central  Google Scholar 

Janmohamed M, Brodie MJ, Kwan P. Pharmacoresistance: epidemiology, mechanisms, and impact on epilepsy treatment. Neuropharmacology. 2020;168:107790.

Article  CAS  PubMed  Google Scholar 

Kwan P, Brodie MJ. Do the third-generation antiseizure medications provide the “magic bullet” for drug-resistant epilepsy? Focus on cenobamate. Epilepsia. 2025;66(Suppl. 1):1–3.

Article  PubMed  PubMed Central  Google Scholar 

Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62(4):375–81.

Article  CAS  PubMed  Google Scholar 

Callaghan BC, Anand K, Hesdorffer D, Hauser WA, French JA. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann Neurol. 2007;62(4):382–9.

Article  PubMed  Google Scholar 

Löscher W, White HS, Klein P. The complexity and challenges of developing effective epilepsy therapies: lessons to be learned from comparing cenobamate, carisbamate and padsevonil. CNS Drugs. (2006). https://doi.org/10.1007/s40263-026-01284-x

Löscher W, Sills GJ, White HS. The ups and downs of alkyl-carbamates in epilepsy therapy: how does cenobamate differ? Epilepsia. 2021;62(3):596–614.

Article  PubMed  Google Scholar 

Moffat JG, Vincent F, Lee JA, Eder J, Prunotto M. Opportunities and challenges in phenotypic drug discovery: an industry perspective. Nat Rev Drug Discov. 2017;16(8):531–43.

Article  CAS  PubMed  Google Scholar 

Vincent F, Nueda A, Lee J, Schenone M, Prunotto M, Mercola M. Phenotypic drug discovery: recent successes, lessons learned and new directions. Nat Rev Drug Discov. 2022;21(12):899–914.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Swinney DC, Anthony J. How were new medicines discovered? Nat Rev Drug Discov. 2011;10(7):507–19.

Article  CAS  PubMed  Google Scholar 

Scannell JW, Bosley J, Hickman JA, Dawson GR, Truebel H, Ferreira GS, et al. Predictive validity in drug discovery: what it is, why it matters and how to improve it. Nat Rev Drug Discov. 2022;21(12):915–31.

Article  CAS  PubMed  Google Scholar 

Swinney DC, Lee JA. Recent advances in phenotypic drug discovery. F1000Research. 2020;9:944.

Article  CAS  Google Scholar 

Eder J, Sedrani R, Wiesmann C. The discovery of first-in-class drugs: origins and evolution. Nat Rev Drug Discov. 2014;13(8):577–87.

Article  CAS  PubMed  Google Scholar 

Gordon R, Bernard P, Pack E, Lee K, Choi YM. Pharmacological profile of YKP10A: a novel antidepressant [abstract no. 583.9]. Soc Neurosci Abstr. 1998;24:1490.

Google Scholar 

Amsterdam JD, Brunswick DJ, Hundert M. A single-site, double-blind, placebo-controlled, dose-ranging study of YKP10A: a putative, new antidepressant. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(7–8):1333–8.

Article  CAS  PubMed  Google Scholar 

Hasan S, Pradervand S, Ahnaou A, Drinkenburg W, Tafti M, Franken P. How to keep the brain awake? The complex molecular pharmacogenetics of wake promotion. Neuropsychopharmacology. 2009;34(7):1625–40.

Article  CAS  PubMed  Google Scholar 

Baladi MG, Forster MJ, Gatch MB, Mailman RB, Hyman DL, Carter LP, et al. Characterization of the neurochemical and behavioral effects of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther. 2018;366(2):367–76.

Article  CAS  PubMed  Google Scholar 

Kilian M, Frey H-H. Central monoamines and convulsive thresholds in mice and rats. Neuropharmacology. 1973;12:681–92.

Article  CAS