Skip to content
2000
image of Cannabidiol against Epilepsy: Insights and an Experimental In Silico Approach

Abstract

Cannabidiol (CBD), one of the compounds found in cannabis sativa, has drawn a lot of interest in the study and treatment of epilepsy. The antiepileptic qualities of CBD are being investigated for their ability to reduce seizure frequency and intensity in people with rare epilepsies, including West syndrome, Ohtahara's syndrome, Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous Sclerosis. This review attempts to analyze the antiepileptic effects of cannabidiol against voltage-gated calcium channel T-type (Ca), Gamma-Aminobutyric Acid A (GABA), voltage-gated potassium channel of the Q family (KCNQ2), voltage-gated sodium channel (Na), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) using techniques. Studies were conducted to investigate Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) parameters, and subsequently, molecular docking was performed. CBD demonstrated good oral absorption and the ability to cross the blood-brain barrier, as indicated by its pharmacokinetic parameters. The CBD may lead to potential drug interactions and increased bioavailability of the molecule due to metabolic interactions with the cytochrome P450 enzymatic system. CBD did not present toxicity parameters evaluated in this work. The molecular docking of CBD showed good interactions with NMDA and Nav. It also demonstrated good binding energy and molecular interactions with these targets, suggesting that these proteins are its main molecular targets.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128392406251110112113
2026-01-22
2026-02-23
Loading full text...

Full text loading...

References

  1. Falco-Walter J. Epilepsy—definition, classification, pathophysiology, and epidemiology. Semin. Neurol. 2020 40 6 617 623 10.1055/s‑0040‑1718719 33155183
    [Google Scholar]
  2. Organization W.H. Epilepsy. 2025 Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy
  3. Fisher R.S. Cross J.H. French J.A. Operational classification of seizure types by the International League Against Epilepsy: Position paper of the ILAE commission for classification and terminology. Epilepsia 2017 58 4 522 530 10.1111/epi.13670 28276060
    [Google Scholar]
  4. Yuen A.W.C. Keezer M.R. Sander J.W. Epilepsy is a neurological and a systemic disorder. Epilepsy Behav. 2018 78 57 61 10.1016/j.yebeh.2017.10.010 29175221
    [Google Scholar]
  5. Falco-Walter J.J. Scheffer I.E. Fisher R.S. The new definition and classification of seizures and epilepsy. Epilepsy Res. 2018 139 73 79 10.1016/j.eplepsyres.2017.11.015 29197668
    [Google Scholar]
  6. Sierra-Paredes G. Sierra-Marcuño G. Extrasynaptic GABA and glutamate receptors in epilepsy. CNS Neurol. Disord. Drug Targets 2007 6 4 288 300 10.2174/187152707781387251 17691986
    [Google Scholar]
  7. Treiman D.M. GABAergic mechanisms in epilepsy. Epilepsia 2001 42 s3 8 12 10.1046/j.1528‑1157.2001.042suppl.3008.x 11520315
    [Google Scholar]
  8. Ghit A. Assal D. Al-Shami A.S. Hussein D.E.E. GABAA receptors: Structure, function, pharmacology, and related disorders. J. Genet. Eng. Biotechnol. 2021 19 1 123 10.1186/s43141‑021‑00224‑0 34417930
    [Google Scholar]
  9. Sarlo G.L. Holton K.F. Brain concentrations of glutamate and GABA in human epilepsy: A review. Seizure 2021 91 213 227 10.1016/j.seizure.2021.06.028 34233236
    [Google Scholar]
  10. French J.A. Krauss G.L. Wechsler R.T. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. Neurology 2015 85 11 950 957 10.1212/WNL.0000000000001930 26296511
    [Google Scholar]
  11. Glauser T.A. Dlugos D.J. Dodson W.E. Grinspan A. Wang S. Wu S.C. Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents. J. Child Neurol. 2007 22 6 693 699 10.1177/0883073807303997 17641254
    [Google Scholar]
  12. Hanada T. Ionotropic glutamate receptors in epilepsy: A review focusing on AMPA and NMDA receptors. Biomolecules 2020 10 3 464 10.3390/biom10030464 32197322
    [Google Scholar]
  13. Oliva M. Berkovic S.F. Petrou S. Sodium channels and the neurobiology of epilepsy. Epilepsia 2012 53 11 1849 1859 10.1111/j.1528‑1167.2012.03631.x 22905747
    [Google Scholar]
  14. Catterall W.A. Kalume F. Oakley J.C. NaV 1.1 channels and epilepsy. J. Physiol. 2010 588 11 1849 1859 10.1113/jphysiol.2010.187484 20194124
    [Google Scholar]
  15. Gross C. Tiwari D. Regulation of ion channels by MicroRNAs and the implication for epilepsy. Curr. Neurol. Neurosci. Rep. 2018 18 9 60 10.1007/s11910‑018‑0870‑2 30046905
    [Google Scholar]
  16. Thijs R.D. Surges R. O’Brien T.J. Sander J.W. Epilepsy in adults. Lancet 2019 393 10172 689 701 10.1016/S0140‑6736(18)32596‑0 30686584
    [Google Scholar]
  17. Sills G.J. Rogawski M.A. Mechanisms of action of currently used antiseizure drugs. Neuropharmacology 2020 168 107966 10.1016/j.neuropharm.2020.107966 32120063
    [Google Scholar]
  18. Castillo-Arellano J. Canseco-Alba A. Cutler S.J. León F. The polypharmacological effects of cannabidiol. Molecules 2023 28 7 3271 10.3390/molecules28073271 37050032
    [Google Scholar]
  19. Arzimanoglou A. Brandl U. Cross J.H. Epilepsy and cannabidiol: A guide to treatment. Epileptic Disord. 2020 22 1 1 14 10.1684/epd.2020.1141 32096470
    [Google Scholar]
  20. Ożarowski M. Karpiński T.M. Zielińska A. Souto E.B. Wielgus K. Cannabidiol in neurological and neoplastic diseases: Latest developments on the molecular mechanism of action. Int. J. Mol. Sci. 2021 22 9 4294 10.3390/ijms22094294 33919010
    [Google Scholar]
  21. Zuardi A.W. History of cannabis as a medicine: A review. Rev. Bras. Psiquiatr. 2006 28 2 153 157 10.1590/S1516‑44462006000200015 16810401
    [Google Scholar]
  22. Sun X. Research Progress on cannabinoids in Cannabis (Cannabis sativa L.) in China. Molecules 2023 28 9 3806 10.3390/molecules28093806 37175216
    [Google Scholar]
  23. Pagano C. Navarra G. Coppola L. Avilia G. Bifulco M. Laezza C. Cannabinoids: Therapeutic use in clinical practice. Int. J. Mol. Sci. 2022 23 6 3344 10.3390/ijms23063344 35328765
    [Google Scholar]
  24. Kirkpatrick M. O’callaghan F. Epilepsy and cannabis: So near, yet so far. Dev. Med. Child Neurol. 2022 64 2 162 167 10.1111/dmcn.15032 34498262
    [Google Scholar]
  25. Neubauer D. Perković Benedik M. Osredkar D. Cannabidiol for treatment of refractory childhood epilepsies: Experience from a single tertiary epilepsy center in Slovenia. Epilepsy Behav. 2018 81 79 85 10.1016/j.yebeh.2018.02.009 29526578
    [Google Scholar]
  26. Samanta D. A scoping review on cannabidiol therapy in tuberous sclerosis: Current evidence and perspectives for future development. Epilepsy Behav. 2022 128 108577 10.1016/j.yebeh.2022.108577 35151190
    [Google Scholar]
  27. Caraballo R. Valenzuela G.R. Cannabidiol-enriched medical cannabis as add-on therapy in children with treatment-resistant West syndrome: A study of eight patients. Seizure 2021 92 238 243 10.1016/j.seizure.2021.10.002 34624613
    [Google Scholar]
  28. Wheless J.W. Fulton S.P. Mudigoudar B.D. Dravet Syndrome: A review of current management. Pediatr. Neurol. 2020 107 28 40 10.1016/j.pediatrneurol.2020.01.005 32165031
    [Google Scholar]
  29. Sullivan J. Wirrell E.C. Dravet syndrome as an example of precision medicine in epilepsy. Epilepsy Curr. 2023 23 1 4 7 10.1177/15357597221106281 36923331
    [Google Scholar]
  30. Anwar A. Saleem S. Patel U.K. Arumaithurai K. Malik P. Dravet syndrome: An overview. Cureus 2019 11 6 e5006 10.7759/cureus.5006 31497436
    [Google Scholar]
  31. Ding J. Li X. Tian H. SCN1A Mutation—beyond dravet syndrome: A systematic review and narrative synthesis. Front. Neurol. 2021 12 743726 10.3389/fneur.2021.743726 35002916
    [Google Scholar]
  32. Myers K.A. SCN1A as a therapeutic target for Dravet syndrome. Expert Opin. Ther. Targets 2023 27 6 459 467 10.1080/14728222.2023.2230364 37364240
    [Google Scholar]
  33. Xu C. Zhang Y. Gozal D. Carney P. Channelopathy of dravet syndrome and potential neuroprotective effects of cannabidiol. J. Cent. Nerv. Syst. Dis. 2021 13 11795735211048045 10.1177/11795735211048045 34992485
    [Google Scholar]
  34. Lagae L. Dravet syndrome. Curr. Opin. Neurol. 2021 34 2 213 218 10.1097/WCO.0000000000000902 33395108
    [Google Scholar]
  35. Wirrell E.C. Hood V. Knupp K.G. International consensus on diagnosis and management of Dravet syndrome. Epilepsia 2022 63 7 1761 1777 10.1111/epi.17274 35490361
    [Google Scholar]
  36. He Z. Li Y. Zhao X. Li B. Dravet syndrome: Advances in etiology, clinical presentation, and treatment. Epilepsy Res. 2022 188 107041 10.1016/j.eplepsyres.2022.107041 36368227
    [Google Scholar]
  37. Pong A.W. Xu K.J. Klein P. Recent advances in pharmacotherapy for epilepsy. Curr. Opin. Neurol. 2023 36 2 77 85 10.1097/WCO.0000000000001144 36762638
    [Google Scholar]
  38. Guan L. Han Y. Yang C. CRISPR-Cas9-mediated gene therapy in neurological disorders. Mol. Neurobiol. 2022 59 2 968 982 10.1007/s12035‑021‑02638‑w 34813019
    [Google Scholar]
  39. Higurashi N Broccoli V Hirose S Genetics and gene therapy in Dravet syndrome. Epilepsy Behav. 2022 131 Pt B 108043 10.1016/j.yebeh.2021.108043 34053869
    [Google Scholar]
  40. Bayat A. Bayat M. Rubboli G. Møller R.S. Epilepsy syndromes in the first year of life and usefulness of genetic testing for precision therapy. Genes 2021 12 7 1051 10.3390/genes12071051 34356067
    [Google Scholar]
  41. Golub V. Reddy D.S. Cannabidiol therapy for refractory epilepsy and seizure disorders. Adv. Exp. Med. Biol. 2021 1264 93 110 10.1007/978‑3‑030‑57369‑0_7 33332006
    [Google Scholar]
  42. Villanueva V. Carreño-Martínez M. Gil Nagel-Rein A. López-González F.J. New therapeutic approach in Dravet syndrome and Lennox-Gastaut syndrome with cannabidiol. Rev. Neurol. 2021 72 S01 S1 S10 10.33588/rn.72S01.2021017 33908026
    [Google Scholar]
  43. von Wrede R. Helmstaedter C. Surges R. Cannabidiol in the treatment of epilepsy. Clin. Drug Investig. 2021 41 3 211 220 10.1007/s40261‑021‑01003‑y 33559102
    [Google Scholar]
  44. Thiele E.A. Bebin E.M. Filloux F. Long‐term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: An open‐label extension trial. Epilepsia 2022 63 2 426 439 10.1111/epi.17150 34957550
    [Google Scholar]
  45. Burke C. Crossan C. Tyas E. Hemstock M. Lee D. Bowditch S. A cost-utility analysis of add-on cannabidiol versus usual care alone for the treatment of seizures associated with tuberous sclerosis complex in england and wales. PharmacoEconom. Open 2024 8 4 611 626 10.1007/s41669‑024‑00474‑x 38441854
    [Google Scholar]
  46. Sekar K. Pack A. Epidiolex as adjunct therapy for treatment of refractory epilepsy: A comprehensive review with a focus on adverse effects. F1000 Res. 2019 8 10.12688/f1000research.16515.1
    [Google Scholar]
  47. Borrelli S. El Tahry R. Therapeutic approach to Lennox–Gastaut syndrome: A systematic review. Acta Neurol. Belg. 2019 119 3 315 324 10.1007/s13760‑019‑01185‑5 31286465
    [Google Scholar]
  48. Asadi-Pooya A.A. Lennox-Gastaut syndrome: A comprehensive review. Neurol. Sci. 2018 39 3 403 414 10.1007/s10072‑017‑3188‑y 29124439
    [Google Scholar]
  49. Smith K.M. Britton J.W. Cascino G.D. Late-onset Lennox-Gastaut syndrome. Neurol. Clin. Pract. 2018 8 5 397 402 10.1212/CPJ.0000000000000527 30564493
    [Google Scholar]
  50. Zhou Z. Jiao X. Gong P. Clinical features and underlying etiology of children with Lennox–Gastaut syndrome. J. Neurol. 2024 271 8 5392 5401 10.1007/s00415‑024‑12465‑3 39008035
    [Google Scholar]
  51. Strzelczyk A. Zuberi S.M. Striano P. Rosenow F. Schubert-Bast S. The burden of illness in Lennox–Gastaut syndrome: a systematic literature review. Orphanet J. Rare Dis. 2023 18 1 42 10.1186/s13023‑023‑02626‑4 36859290
    [Google Scholar]
  52. Yang M.H. Liu J. Zhou Y.L. Asymmetric slow-spike-wave patterns with maximal discharges contralateral to mri lesions predict better surgical prognosis in symptomatic lennox-gastaut syndrome or lennox-gastaut phenotypes. Pediatr. Neurosurg. 2020 55 1 26 35 10.1159/000504513 31851997
    [Google Scholar]
  53. Nelson J.A. Knupp K.G. Lennox-gastaut syndrome: Current treatments, novel therapeutics, and future directions. Neurotherapeutics 2023 20 5 1255 1262 10.1007/s13311‑023‑01397‑x 37353676
    [Google Scholar]
  54. Sullivan J. Benítez A. Roth J. A systematic literature review on the global epidemiology of Dravet syndrome and Lennox–Gastaut syndrome: Prevalence, incidence, diagnosis, and mortality. Epilepsia 2024 65 5 1240 1263 10.1111/epi.17866 38252068
    [Google Scholar]
  55. Cai K. Wang J. Eissman J. A missense mutation in SLC6A1 associated with Lennox-Gastaut syndrome impairs GABA transporter 1 protein trafficking and function. Exp. Neurol. 2019 320 112973 10.1016/j.expneurol.2019.112973 31176687
    [Google Scholar]
  56. Zhang L. Wang J. Wang C. Efficacy and safety of antiseizure medication for Lennox–Gastaut syndrome: A systematic review and network meta‐analysis. Dev. Med. Child Neurol. 2022 64 3 305 313 10.1111/dmcn.15072 34590711
    [Google Scholar]
  57. Chen J.W. Borgelt L.M. Blackmer A.B. Cannabidiol: A new hope for patients with dravet or lennox-gastaut syndromes. Ann. Pharmacother. 2019 53 6 603 611 10.1177/1060028018822124 30616356
    [Google Scholar]
  58. Devinsky O. Patel A.D. Cross J.H. Effect of cannabidiol on drop seizures in the lennox–gastaut syndrome. N. Engl. J. Med. 2018 378 20 1888 1897 10.1056/NEJMoa1714631 29768152
    [Google Scholar]
  59. Thiele E.A. Marsh E.D. French J.A. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018 391 10125 1085 1096 10.1016/S0140‑6736(18)30136‑3 29395273
    [Google Scholar]
  60. Wang C. Wang Y. Xu W. Generation of an induced pluripotent stem cell line from an Ohtahara syndrome patient with the hemizygous mutation p.Q503Afs*28 (c.1507_1508del) in the ARX gene. Stem Cell Res. (Amst.) 2022 59 102621 10.1016/j.scr.2021.102621 34968892
    [Google Scholar]
  61. Ohtahara S. Early Infantile Epileptic Encephalopathy with Suppression-Bursts. Epileptic Syndromes in Infancy, Childhood and Adolescence. John Libbey Eurotext ltd 1992 25 34
    [Google Scholar]
  62. Malik S.I. Galliani C.A. Hernandez A.W. Donahue D.J. Epilepsy surgery for early infantile epileptic encephalopathy (ohtahara syndrome). J. Child Neurol. 2013 28 12 1607 1617 10.1177/0883073812464395 23143728
    [Google Scholar]
  63. Saitsu H. Kato M. Matsumoto N. Haploinsufficiency of STXBP1 and Ohtahara syndrome. Jasper’s Basic Mechanisms of the Epilepsies. Oxford Academic 2012 824 834 10.1093/med/9780199746545.003.0064
    [Google Scholar]
  64. Esposito A. Falace A. Wagner M. Biallelic DMXL2 mutations impair autophagy and cause Ohtahara syndrome with progressive course. Brain 2019 142 12 3876 3891 10.1093/brain/awz326 31688942
    [Google Scholar]
  65. Costain G. Walker S. Argiropoulos B. Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders. J. Neurodev. Disord. 2019 11 1 3 10.1186/s11689‑019‑9263‑3 30732576
    [Google Scholar]
  66. Williams A.N. Gray R.G. MPhil KP, MRCPath PR, Whitehouse WPA. A case of Ohtahara syndrome with cytochrome oxidase deficiency. Dev. Med. Child Neurol. 1998 40 8 568 570 10.1111/j.1469‑8749.1998.tb15416.x 9746010
    [Google Scholar]
  67. Singhi P. Ray M. Ohtahara syndrome with biotinidase deficiency. J. Child Neurol. 2011 26 4 507 509 10.1177/0883073810383018 21115748
    [Google Scholar]
  68. Kodera H. Ohba C. Kato M. De novo GABRA1 mutations in Ohtahara and West syndromes. Epilepsia 2016 57 4 566 573 10.1111/epi.13344 26918889
    [Google Scholar]
  69. Uysal S.P. Sahi̇n M. Tuberous sclerosis: a review of the past, present, and future. Turk. J. Med. Sci. 2020 50 7 1665 1676 10.3906/sag‑2002‑133 32222129
    [Google Scholar]
  70. Touraine R Hauet Q Harzallah I Baruteau A-E Tuberous sclerosis complex: Genetic counselling and perinatal follow-up. Arch Pediatr. 2022 29 5S3 10.1016/S0929‑693X(22)00283‑4
    [Google Scholar]
  71. Marcinkowska A.B. Tarasewicz A. Jóźwiak S. Dębska-Ślizień A. Szurowska E. Tuberous sclerosis complex-associated neuropsychiatric disorders. Psychiatr. Pol. 2022 1 20 10.12740/PP/OnlineFirst/146265 36370437
    [Google Scholar]
  72. Pfirmann P. Combe C. Rigothier C. Tuberous sclerosis complex: A review. Rev. Med. Interne 2021 42 10 714 721 10.1016/j.revmed.2021.03.003 33836894
    [Google Scholar]
  73. Portocarrero L.K.L. Quental K.N. Samorano L.P. de Oliveira Z.N.P. Rivitti-Machado M.C da M. Tuberous sclerosis complex: Review based on new diagnostic criteria. An. Bras. Dermatol. 2018 93 323 331 10.1590/abd1806‑4841.20186972
    [Google Scholar]
  74. Uliel-Sibony S. Chernuha V. Meirson H. Fattal-Valevski A. Medical treatment of tuberous sclerosis-related epilepsy. Childs Nerv. Syst. 2020 36 10 2511 2517 10.1007/s00381‑020‑04772‑7 32829444
    [Google Scholar]
  75. Singh A. Hadjinicolaou A. Peters J.M. Salussolia C.L. Treatment-resistant epilepsy and tuberous sclerosis complex: Treatment, maintenance, and future directions. Neuropsychiatr. Dis. Treat. 2023 19 733 748 10.2147/NDT.S347327 37041855
    [Google Scholar]
  76. Specchio N. Nabbout R. Aronica E. Updated clinical recommendations for the management of tuberous sclerosis complex associated epilepsy. Eur. J. Paediatr. Neurol. 2023 47 25 34 10.1016/j.ejpn.2023.08.005 37669572
    [Google Scholar]
  77. Aronica E. Specchio N. Luinenburg M.J. Curatolo P. Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy. Brain 2023 146 7 2694 2710 10.1093/brain/awad048 36806388
    [Google Scholar]
  78. Weinstock A. Bebin E.M. Checketts D. Long‐term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3‐year results from the cannabidiol expanded access program. Epilepsia Open 2024 9 5 1816 1825 10.1002/epi4.13013 39088193
    [Google Scholar]
  79. Sharma S. Sharma S. “West Syndrome—Infantile Spasms”: A pediatric case report. Int. J. Clin. Pediatr. Dent. 2021 14 2 323 326 10.5005/jp‑journals‑10005‑1922 34413615
    [Google Scholar]
  80. Dias Freitas F. Cavaco Raposo S. Luis Nogueira A. West syndrome and the importance of routine physical examinations and parental education: A case report. Cureus 2022 14 11 e31848 10.7759/cureus.31848 36579257
    [Google Scholar]
  81. Pavone P. Polizzi A. Marino S.D. West syndrome: A comprehensive review. Neurol. Sci. 2020 41 12 3547 3562 10.1007/s10072‑020‑04600‑5 32827285
    [Google Scholar]
  82. Jia J.L. Chen S. Sivarajah V. Stephens D. Cortez M.A. Latitudinal differences on the global epidemiology of infantile spasms: systematic review and meta-analysis. Orphanet J. Rare Dis. 2018 13 1 216 10.1186/s13023‑018‑0952‑x 30486850
    [Google Scholar]
  83. Lux A.L. Latest American and European updates on infantile spasms. Curr. Neurol. Neurosci. Rep. 2013 13 3 334 10.1007/s11910‑012‑0334‑z 23341252
    [Google Scholar]
  84. Osborne J.P. Edwards S.W. Dietrich Alber F. The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS). Epilepsia 2019 60 9 1861 1869 10.1111/epi.16305 31418851
    [Google Scholar]
  85. Tang X. Jaenisch R. Sur M. The role of GABAergic signalling in neurodevelopmental disorders. Nat. Rev. Neurosci. 2021 22 5 290 307 10.1038/s41583‑021‑00443‑x 33772226
    [Google Scholar]
  86. Pracucci E. Pillai V. Lamers D. Parra R. Landi S. Neuroinflammation: A Signature or a Cause of Epilepsy? Int. J. Mol. Sci. 2021 22 13 6981 10.3390/ijms22136981 34209535
    [Google Scholar]
  87. Gilliam F.G. Hecimovic H. Gentry M.S. Serotonergic therapy in epilepsy. Curr. Opin. Neurol. 2021 34 2 206 212 10.1097/WCO.0000000000000901 33664206
    [Google Scholar]
  88. Becker L.L. Kaindl A.M. Corticosteroids in childhood epilepsies: A systematic review. Front. Neurol. 2023 14 1142253 10.3389/fneur.2023.1142253 36970534
    [Google Scholar]
  89. Henriques-Souza A.M de M. Ataide Junior L, Laurentino SG. Arq. Neuropsiquiatr. 2007 65 144 149 10.1590/S0004‑282X2007000100029 17420838
    [Google Scholar]
  90. Ghasemi M. Schachter S.C. The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav. 2011 22 4 617 640 10.1016/j.yebeh.2011.07.024 22056342
    [Google Scholar]
  91. Sanz P. Rubio T. Garcia-Gimeno M.A. Neuroinflammation and Epilepsy: From Pathophysiology to Therapies Based on Repurposing Drugs. Int. J. Mol. Sci. 2024 25 8 4161 10.3390/ijms25084161 38673747
    [Google Scholar]
  92. Myung Y. de Sá A.G.C. Ascher D.B. Deep-PK: deep learning for small molecule pharmacokinetic and toxicity prediction. Nucleic Acids Res. 2024 52 W1 W469-75 10.1093/nar/gkae254 38634808
    [Google Scholar]
  93. MarvinSketch MarvinSketch. ChemAxon 2023
    [Google Scholar]
  94. Gangwar S.P. Yen L.Y. Yelshanskaya M.V. Korman A. Jones D.R. Sobolevsky A.I. Modulation of GluA2–γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2. Nat. Struct. Mol. Biol. 2023 30 10 1481 1494 10.1038/s41594‑023‑01080‑x 37653241
    [Google Scholar]
  95. Chen Z. Mondal A. Minor D.L. Structural basis for CaVα2δ: gabapentin binding. Nat. Struct. Mol. Biol. 2023 30 6 735 739 10.1038/s41594‑023‑00951‑7 36973510
    [Google Scholar]
  96. Kim J.J. Gharpure A. Teng J. Shared structural mechanisms of general anaesthetics and benzodiazepines. Nature 2020 585 7824 303 308 10.1038/s41586‑020‑2654‑5 32879488
    [Google Scholar]
  97. Li X. Zhang Q. Guo P. Molecular basis for ligand activation of the human KCNQ2 channel. Cell Res. 2021 31 1 52 61 10.1038/s41422‑020‑00410‑8 32884139
    [Google Scholar]
  98. Fan X. Huang J. Jin X. Yan N. Cryo-EM structure of human voltage-gated sodium channel Na v 1.6. Proc. Natl. Acad. Sci. USA 2023 120 5 e2220578120 10.1073/pnas.2220578120 36696443
    [Google Scholar]
  99. Wang H. Lv S. Stroebel D. Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors. Neuron 2021 109 15 2443 2456.e5 10.1016/j.neuron.2021.05.031 34186027
    [Google Scholar]
  100. Molegro Virtual Docker 6.0.1. CLC Bio Company. 2013
    [Google Scholar]
  101. Dassault Systèmes B.I.O.V.I.A. Discovery Studio Visualizer. Dassault Systèmes 2019
    [Google Scholar]
  102. Komura H. Watanabe R. Mizuguchi K. The trends and future prospective of in silico models from the viewpoint of ADME evaluation in drug discovery. Pharmaceutics 2023 15 11 2619 10.3390/pharmaceutics15112619 38004597
    [Google Scholar]
  103. Pushpakom S. Iorio F. Eyers P.A. Drug repurposing: Progress, challenges and recommendations. Nat. Rev. Drug Discov. 2019 18 1 41 58 10.1038/nrd.2018.168 30310233
    [Google Scholar]
  104. Zhang Z. Tang W. Drug metabolism in drug discovery and development. Acta Pharm. Sin. B 2018 8 5 721 732 10.1016/j.apsb.2018.04.003 30245961
    [Google Scholar]
  105. Verma S. Goand U.K. Husain A. Katekar R.A. Garg R. Gayen J.R. Challenges of peptide and protein drug delivery by oral route: Current strategies to improve the bioavailability. Drug Dev. Res. 2021 82 7 927 944 10.1002/ddr.21832 33988872
    [Google Scholar]
  106. Husain A. Makadia V. Valicherla G.R. Riyazuddin M. Gayen J.R. Approaches to minimize the effects of P‐glycoprotein in drug transport: A review. Drug Dev. Res. 2022 83 4 825 841 10.1002/ddr.21918 35103340
    [Google Scholar]
  107. Teleanu R.I. Preda M.D. Niculescu A.G. Current strategies to enhance delivery of drugs across the blood–brain barrier. Pharmaceutics 2022 14 5 987 10.3390/pharmaceutics14050987 35631573
    [Google Scholar]
  108. Pantaleão S.Q. Fernandes P.O. Gonçalves J.E. Maltarollo V.G. Honorio K.M. Recent advances in the prediction of pharmacokinetics properties in drug design studies: A review. ChemMedChem 2022 17 1 e202100542 10.1002/cmdc.202100542 34655454
    [Google Scholar]
  109. Fanni D. Pinna F. Gerosa C. Anatomical distribution and expression of CYP in humans: Neuropharmacological implications. Drug Dev. Res. 2021 82 5 628 667 10.1002/ddr.21778 33533102
    [Google Scholar]
  110. Zhao M. Ma J. Li M. Cytochrome P450 enzymes and drug metabolism in humans. Int. J. Mol. Sci. 2021 22 23 12808 10.3390/ijms222312808 34884615
    [Google Scholar]
  111. Idrees H. Zaidi S.Z.J. Sabir A. Khan R.U. Zhang X. Hassan S. A review of biodegradable natural polymer-based nanoparticles for drug delivery applications. Nanomaterials 2020 10 10 1970 10.3390/nano10101970 33027891
    [Google Scholar]
  112. Prieto-Martínez F.D. Arciniega M. Medina-Franco J.L. Prieto-Martínez F.D. Arciniega M. Medina-Franco J.L. Molecular docking: Current advances and challenges. TIP J Special Chem Biol Sci 2018 21 10.22201/fesz.23958723e.2018.0.143
    [Google Scholar]
  113. Yelshanskaya M.V. Singh A.K. Sampson J.M. Narangoda C. Kurnikova M. Sobolevsky A.I. Structural bases of noncompetitive inhibition of ampa-subtype ionotropic glutamate receptors by antiepileptic drugs. Neuron 2016 91 6 1305 1315 10.1016/j.neuron.2016.08.012 27618672
    [Google Scholar]
  114. Gumerov V.M. Andrianova E.P. Matilla M.A. Amino acid sensor conserved from bacteria to humans. Proc. Natl. Acad. Sci. USA 2022 119 10 e2110415119 10.1073/pnas.2110415119 35238638
    [Google Scholar]
  115. Scotti L. Lustoza Rodrigues T.C.M. de Sousa N.F. dos Santos A.M.F. Aires Guimarães R.D. Scotti M.T. Challenges and discoveries in polypharmacology of neurodegenerative diseases. Curr. Top. Med. Chem. 2023 23 5 349 370 10.2174/1568026623666230126112628 36703583
    [Google Scholar]
  116. Rodrigues T.C.M.L. Dias A.L. dos Santos A.M.F. Multi-target phenylpropanoids against epilepsy. Curr. Neuropharmacol. 2024 22 13 2168 2190 10.2174/1570159X22666240524160126 38847378
    [Google Scholar]
  117. Valipour M. Naderi N. Heidarli E. Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: A comprehensive in silico, in vitro, and in vivo study. Eur. J. Pharm. Sci. 2021 166 May 105974 10.1016/j.ejps.2021.105974 34390829
    [Google Scholar]
  118. Rampogu S. Park S.J. Lee K.W. Identification of novel scaffolds with dual role as antiepileptic and anti-breast cancer. IEEE/ACM Trans. Comput. Biol. Bioinformatics 2019 16 5 1663 1674 10.1109/TCBB.2018.2855138 30334765
    [Google Scholar]
  119. Türkeş C. Arslan M. Demir Y. Çoçaj L. Rifati Nixha A. Beydemir Ş. Synthesis, biological evaluation and in silico studies of novel N-substituted phthalazine sulfonamide compounds as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg. Chem. 2019 89 103004 10.1016/j.bioorg.2019.103004 31129502
    [Google Scholar]
  120. Sánchez Montero J.M. Agis-Torres A. Solano D. Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer’s disease. Eur. J. Pharmacol. 2021 895 173875 10.1016/j.ejphar.2021.173875 33460612
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128392406251110112113
Loading
/content/journals/cpd/10.2174/0113816128392406251110112113
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.


  • Article Type:
    Review Article
Keywords: Epileptic syndromes ; GABAA ; KCNQ2 ; cannabidiol ; molecular docking ; AMPA ; NaV
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test