Skip to content
2000
Volume 21, Issue 8
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646

Abstract

Epilepsy is a growing concern for the scientific community globally as less than 80% of individuals experience reduced seizure severity with existing antiepileptic medications and the chances of relapses are very high with those medications. Therefore, the existing problem requires more attention to unravel the chances of relapses and adverse effects of available medications. Isoindole-1,3-diones serve as a valuable scaffold with diverse biological activities, including analgesic, anti-inflammatory, and hypolipidemic properties. This review will emphasize the antiepileptic behaviours of the Isoindole-1,3-diones with diversified synthetic procedures and modes of action. For this purpose, an extensive literature survey was undertaken through different online platforms such as PubMed, Web of Science, Scopus, SciFinder, Google Scholar, Science Direct, . Some N-substituted Isoindole-1,3-diones have demonstrated promising anticonvulsant activity, primarily by effectively blocking sodium channels. Epilepsy is often linked to channelopathies involving α, and β-subunits, and medications have specific mechanisms for binding with the α-subunit of the sodium channel. Analyzing the structural features of phenytoin, carbamazepine, and lamotrigine revealed that benzene or phenol substitution, along with the addition of a chloro group, enhances their activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) tests. This review focuses on the role of specific sodium channels in electrical signalling and neurological conditions, emphasizing the significance of Isoindole-1,3-diones and their derivatives in designing potent anticonvulsant agents, particularly in the development of selective sodium channel inhibitors.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cbc/10.2174/0115734072306875241118105536
2024-10-17
2025-10-13

  • From This Site

    /content/journals/cbc/10.2174/0115734072306875241118105536
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AfrikanovaT. SerruysA.S.K. BuenafeO.E.M. ClinckersR. SmoldersI. de WitteP.A.M. CrawfordA.D. EsguerraC.V. Validation of the zebrafish pentylenetetrazol seizure model: Locomotor versus electrographic responses to antiepileptic drugs.PLoS One201381e5416610.1371/journal.pone.0054166 23342097
     [Google Scholar]
  2. SørensenA.T. KokaiaM. Novel approaches to epilepsy treatment.Epilepsia201354111010.1111/epi.12000 23106744
     [Google Scholar]
  3. BrodieM.J. Antiepileptic drug therapy the story so far.Seizure2010191065065510.1016/j.seizure.2010.10.027 21075011
     [Google Scholar]
  4. SinhaR. SaraU.V.S. KhosaR.L. StablesJ. JainJ. Nicotinic acid hydrazones: A novel anticonvulsant pharmacophore.Med. Chem. Res.20112091499150410.1007/s00044‑010‑9396‑0
     [Google Scholar]
  5. JainJ. KumarY. StablesJ. SinhaR. Menthone semicarbazides and thiosemicarbazides as anticonvulsant agents.Med. Chem.201061445010.2174/157340610791208727 20402660
     [Google Scholar]
  6. JonesG.L. WoodburyD.M. Anticonvulsant structure‐activity relationships: Historical development and probable causes of failure.Drug Dev. Res.19822433335510.1002/ddr.430020402
     [Google Scholar]
  7. TafazoliS. O’BrienP.J. Peroxidases: A role in the metabolism and side effects of drugs.Drug Discov. Today200510961762510.1016/S1359‑6446(05)03394‑5 15894226
     [Google Scholar]
  8. ChackalamannilS. RotellaD.P. WardS.E. Comprehensive Medicinal Chemistry III.Elsevier201710.1016/C2014‑1‑02188‑6
     [Google Scholar]
  9. De Lahunta.A. GlassE. KentM. The neurologic examination. de Lahunta’s Veterinary Neuroanatomy and Clinical Neurology.20215314610.1016/B978‑0‑323‑69611‑1.00021‑9
     [Google Scholar]
  10. SilversteinD.C. HopperK. Small animal critical care medicine, second edition. Small Animal Critical Care Medicine, Second Edition.20141113010.1016/B978‑1‑4557‑0306‑7.00212‑9
     [Google Scholar]
  11. BailleuxV. ValléeL. NuytsJ.P. VamecqJ. Anticonvulsant activity of some 4-amino-N-phenylphthalimides and N-(3-amino-2-methylphenyl)phthalimides.Biomed. Pharmacother.19944829510110.1016/0753‑3322(94)90083‑3 7919112
     [Google Scholar]
  12. BailleuxV. ValléeL. NuytsJ.P. VamecqJ. Original anticonvulsant properties of two N-phenylphthalimide derivatives.Biomed. Pharmacother.1993471046346410.1016/0753‑3322(93)90345‑L 8061248
     [Google Scholar]
  13. VamecqJ. BacP. HerrenknechtC. MauroisP. DelcourtP. StablesJ.P. Synthesis and anticonvulsant and neurotoxic properties of substituted N-phenyl derivatives of the phthalimide pharmacophore.J. Med. Chem.20004371311131910.1021/jm990068t 10753468
     [Google Scholar]
  14. WiȩcekM. Kieć-KononowiczK. Synthesis and anticonvulsant evaluation of some N-substituted phthalimides.Acta Pol. Pharm.2009663249257 19645325
     [Google Scholar]
  15. BailleuxV. ValleeL. NuytsJ.P. VamecqJ. Synthesis and anticonvulsant activity of some N-phenylphthalimides.Chem. Pharm. Bull. (Tokyo)19944291817182110.1248/cpb.42.1817 7954932
     [Google Scholar]
  16. BailleuxV. ValléeL. NuytsJ.P. HamoirG. PoupaertJ.H. StablesJ.P. VamecqJ. Synthesis and anticonvulsant activity of some 4-nitro-N-phenylbenzamides.Eur. J. Med. Chem.199530543944410.1016/0223‑5234(96)88254‑7 22625428
     [Google Scholar]
  17. AndreichikovY.S. ZalesovV.V. PodushkinaN.A. Synthesis and biological activity of amides of ω-(phthalimido)-alkyl carboxylic acids.Pharm. Chem. J.19801429910410.1007/BF00765906
     [Google Scholar]
  18. BhowmickS. Synthesis and anticonvulsant activity of N-phthaloyl GABA - A new GABA derivative.Indian J. Exp. Biol.1989279805808 2632400
     [Google Scholar]
  19. HabibuddinM. Neuropharmacology of amide derivatives of P-GABA.Indian J. Exp. Biol.1992307578582
     [Google Scholar]
  20. UsifohC.O. LambertD.M. WoutersJ. ScribaG.K.E. Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids.Arch. Pharm.200133410323331 11759171
     [Google Scholar]
  21. YadavN. MalhotraM. MongaV. SharmaS. JainJ. SamadA. DeepA. Synthesis, characterization, and pharmacological evaluation of new GABA analogs as potent anticonvulsant agents.Med. Chem. Res.20122192208221610.1007/s00044‑011‑9743‑9
     [Google Scholar]
  22. RagavendranJ.V. SriramD. PatelS.K. ReddyI.V. BharathwajanN. StablesJ. YogeeswariP. Design and synthesis of anticonvulsants from a combined phthalimide–GABA–anilide and hydrazone pharmacophore.Eur. J. Med. Chem.200742214615110.1016/j.ejmech.2006.08.010 17011080
     [Google Scholar]
  23. GanwirP. JaydeokarS. ChaturbhujG.U. Phthaloylation of amines, hydrazines, and hydrazides by N-substituted phthalimides using recyclable sulfated polyborate.Results Chem.2022410029310.1016/j.rechem.2022.100293
     [Google Scholar]
  24. JelaliH. MansourL. DeniauE. SauthierM. HamdiN. An efficient synthesis of phthalimides and their biological activities.Polycycl. Aromat. Compd.20224241806181310.1080/10406638.2020.1809468
     [Google Scholar]
  25. Tabatabaei RafieiL.S. AsadiM. HosseiniF.S. AmanlouA. BiglarM. AmanlouM. Synthesis and evaluation of anti-epileptic properties of new phthalimide-4,5-dihydrothiazole-amide derivatives.Polycycl. Aromat. Compd.20224241271128110.1080/10406638.2020.1776345
     [Google Scholar]
  26. SoyerZ. KılıcF.S. ErolK. PabuccuogluV. The synthesis and anticonvulsant activity of some ω-phthalimido-N-phenylacetamide and propionamide derivatives.Arch. Pharm. (Weinheim)2004337210511110.1002/ardp.200300823 14981667
     [Google Scholar]
  27. khademi, M.; Moradkhani, F.; Hosseini, F.S.; Asadi, M.; Amanlou, A.; Khorasani, R.; Morgani, A.B.; Amanlou, M. Synthesis, molecular docking, and antiepileptic activity of new N-phthaloylglycine derivatives.J. Indian Chem. Soc.20221962467247410.1007/s13738‑021‑02467‑7
     [Google Scholar]
  28. AmanlouM. AsadollahiA. AsadiM. HosseiniF.S. EkhtiariZ. BiglarM. Synthesis, molecular docking, and antiepileptic activity of novel phthalimide derivatives bearing amino acid conjugated anilines.Res. Pharm. Sci.201914653454310.4103/1735‑5362.272562 32038733
     [Google Scholar]
  29. DavoodA. ImanM. PouriaieeH. ShafaroodiH. AkhbariS. AzimidoostL. ImaniE. RahmatpourS. Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models.Iran. J. Basic Med. Sci.201720443043710.22038/ijbms.2017.8586 28804613
     [Google Scholar]
  30. JefferysJ.G.R. Models and mechanisms of experimental epilepsies.Epilepsia200344S12445010.1111/j.0013‑9580.2003.12004.x
     [Google Scholar]
  31. HodgkinA.L. HuxleyA.F. The dual effect of membrane potential on sodium conductance in the giant axon of Loligo.J. Physiol.1952116449750610.1113/jphysiol.1952.sp004719 14946715
     [Google Scholar]
  32. HodgkinA.L. HuxleyA.F. The components of membrane conductance in the giant axon of Loligo.J. Physiol.1952116447349610.1113/jphysiol.1952.sp004718 14946714
     [Google Scholar]
  33. ClareJ.J. TateS.N. NobbsM. RomanosM.A. Voltage-gated sodium channels as therapeutic targets.Drug Discov. Today200051150652010.1016/S1359‑6446(00)01570‑1 11084387
     [Google Scholar]
  34. HodgkinA.L. HuxleyA.F. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo.J. Physiol.1952116444947210.1113/jphysiol.1952.sp004717 14946713
     [Google Scholar]
  35. WangQ. ShenJ. LiZ. TimothyK. VincentG.M. PrioriS.G. SchwartzP.J. KeatingM.T. Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia.Hum. Mol. Genet.1995491603160710.1093/hmg/4.9.1603 8541846
     [Google Scholar]
  36. Campos-RodríguezC. Trujillo-FerraraJ.G. Alvarez-GuerraA. VargasI.M.C. Cuevas-HernándezR.I. Andrade-JorgeE. ZamudioS. JuanE.R.S. Neuropharmacological screening of chiral and non-chiral phthalimide- containing compounds in mice: In vivo and in silico Experiments.Med. Chem.201915110211810.2174/1573406414666180525082038 29793411
     [Google Scholar]
  37. KurmiR.K. SinhaR. AgrawalA. SrivastavaS. In-silico studies on phthalimide GABA analogs for anticonvulsant activity against sodium channel and GABA-AT.Int. J. Pharm. Educ. Res.2023511510.37021/ijper.v5i1.01
     [Google Scholar]
  38. AhujaS. MukundS. DengL. KhakhK. ChangE. HoH. ShriverS. YoungC. LinS. JohnsonJ.P.Jr WuP. LiJ. CoonsM. TamC. BrillantesB. SampangH. MortaraK. BowmanK.K. ClarkK.R. EstevezA. XieZ. VerschoofH. GrimwoodM. DehnhardtC. AndrezJ.C. FockenT. SutherlinD.P. SafinaB.S. StarovasnikM.A. OrtwineD.F. FrankeY. CohenC.J. HackosD.H. KothC.M. PayandehJ. Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist.Science20153506267aac546410.1126/science.aac5464 26680203
     [Google Scholar]
  39. CatterallW.A. GoldinA.L. WaxmanS.G. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.Pharmacol. Rev.200557439740910.1124/pr.57.4.4 16382098
     [Google Scholar]
  40. GoldinA.L. Resurgence of sodium channel research.Annu. Rev. Physiol.200163187189410.1146/annurev.physiol.63.1.871 11181979
     [Google Scholar]
  41. SarmastS.T. AbdullahiA.M. JahanN. Current classification of seizures and epilepsies: Scope, limitations and recommendations for future action.Cureus2020129e1054910.7759/cureus.10549 33101797
     [Google Scholar]
  42. FisherR.S. BonnerA.M. The revised definition and classification of epilepsy for neurodiagnostic technologists.Neurodiagn. J.201858111010.1080/21646821.2018.1428455 29562876
     [Google Scholar]
  43. FisherR.S. An overview of the 2017 ILAE operational classification of seizure types.Epilepsy Behav.20177027127310.1016/j.yebeh.2017.03.022
     [Google Scholar]
  44. BrodieM.J. ZuberiS.M. SchefferI.E. FisherR.S. The 2017 ILAE classification of seizure types and the epilepsies: What do people with epilepsy and their caregivers need to know?Epileptic Disord.2018202778710.1684/epd.2018.0957 29620013
     [Google Scholar]
  45. RémiJ. Silva CunhaJ.P. VollmarC. Bilgin TopçuoğluÖ. MeierA. UlowetzS. BelezaP. NoachtarS. Quantitative movement analysis differentiates focal seizures characterized by automatisms.Epilepsy Behav.201120464264710.1016/j.yebeh.2011.01.020 21458386
     [Google Scholar]
  46. HamerH.M. LüdersH.O. KnakeS. FritschB. OertelW.H. RosenowF. Electrophysiology of focal clonic seizures in humans: A study using subdural and depth electrodes.Brain2003126354755510.1093/brain/awg051 12566276
     [Google Scholar]
  47. ZhaoJ. AfraP. AdamolekunB. Partial epilepsy presenting as focal atonic seizure: A case report.Seizure201019632632910.1016/j.seizure.2010.04.014 20627778
     [Google Scholar]
  48. RamachandranNairR. OchiA. ImaiK. BeniflaM. AkiyamaT. HolowkaS. RutkaJ.T. Snead O.C.III OtsuboH. Epileptic spasms in older pediatric patients: MEG and ictal high-frequency oscillations suggest focal-onset seizures in a subset of epileptic spasms.Epilepsy Res.2008782-321622410.1016/j.eplepsyres.2007.12.007 18215506
     [Google Scholar]
  49. DobesbergerJ. RistićA.J. WalserG. KuchukhidzeG. UnterbergerI. HöflerJ. AmannE. TrinkaE. Duration of focal complex, secondarily generalized tonic–clonic, and primarily generalized tonic–clonic seizures — A video-EEG analysis.Epilepsy Behav.20154911111710.1016/j.yebeh.2015.03.023 25935513
     [Google Scholar]
  50. UsuiN. KotagalP. MatsumotoR. KellinghausC. LüdersH.O. Focal semiologic and electroencephalographic features in patients with juvenile myoclonic epilepsy.Epilepsia200546101668167610.1111/j.1528‑1167.2005.00262.x 16190941
     [Google Scholar]
  51. GlasstetterM. BöttcherS. ZablerN. EpitashviliN. DümpelmannM. RichardsonM.P. Schulze‐bonhageA. Identification of ictal tachycardia in focal motor- and non-motor seizures by means of a wearable PPG sensor.Sensors20212118601710.3390/s21186017
     [Google Scholar]
  52. GilboaT. Emotional stress–induced seizures: Another reflex epilepsy?Epilepsia2012532e29e3210.1111/j.1528‑1167.2011.03342.x 22150553
     [Google Scholar]
  53. VingerhoetsG. Cognitive effects of seizures.Seizure200615422122610.1016/j.seizure.2006.02.012 16546410
     [Google Scholar]
  54. TangS. AddisL. SmithA. ToppS.D. PendziwiatM. MeiD. ParkerA. AgrawalS. HughesE. LascellesK. WilliamsR.E. FallonP. RobinsonR. CrossH.J. HedderlyT. EltzeC. KerrT. DesurkarA. HussainN. KinaliM. BagnascoI. VassalloG. WhitehouseW. GoyalS. AbsoudM. MøllerR.S. HelbigI. WeberY.G. MariniC. GuerriniR. SimpsonM.A. PalD.K. Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures.Epilepsia2020615995100710.1111/epi.16508 32469098
     [Google Scholar]
  55. KnottC. PanayiotopoulosC.P. Carbamazepine in the treatment of generalised tonic clonic seizures in juvenile myoclonic epilepsy.J. Neurol. Neurosurg. Psychiatry199457450310.1136/jnnp.57.4.503 8164005
     [Google Scholar]
  56. PanayiotopoulosC.P. Typical absence seizures and their treatment.Arch. Dis. Child.199981435135510.1136/adc.81.4.351 10490445
     [Google Scholar]
  57. GiannakodimosS. PanayiotopoulosC.P. Eyelid myoclonia with absences in adults: A clinical and video-EEG study.Epilepsia1996371364410.1111/j.1528‑1157.1996.tb00509.x 8603622
     [Google Scholar]
  58. MasudaH. ShariffE. TohyamaJ. MurakamiH. KameyamaS. Clinical patterns and pathophysiology of hypermotor seizures: An ictal SPECT study.Epileptic Disord.2012141324010.1684/epd.2012.0485 22433234
     [Google Scholar]
  59. WangY. JonesP.J. BattsT.W. LandryV. PatelM.K. BrownM.L. Ligand-based design and synthesis of novel sodium channel blockers from a combined phenytoin–lidocaine pharmacophore.Bioorg. Med. Chem.200917197064707210.1016/j.bmc.2008.10.031 19346132
     [Google Scholar]
  60. StühmerW. ContiF. SuzukiH. WangX. NodaM. YahagiN. KuboH. NumaS. Structural parts involved in activation and inactivation of the sodium channel.Nature1989339622659760310.1038/339597a0 2543931
     [Google Scholar]
  61. BosmansF. Martin-EauclaireM.F. SwartzK.J. Deconstructing voltage sensor function and pharmacology in sodium channels.Nature2008456721920220810.1038/nature07473 19005548
     [Google Scholar]
  62. WestJ.W. PattonD.E. ScheuerT. WangY. GoldinA.L. CatterallW.A. A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.Proc. Natl. Acad. Sci. USA19928922109101091410.1073/pnas.89.22.10910 1332060
     [Google Scholar]
  63. VassilevP.M. ScheuerT. CatterallW.A. Identification of an intracellular peptide segment involved in sodium channel inactivation.Science198824148731658166110.1126/science.2458625 2458625
     [Google Scholar]
  64. VassilevP. ScheuerT. CatterallW.A. Inhibition of inactivation of single sodium channels by a site-directed antibody.Proc. Natl. Acad. Sci. USA198986208147815110.1073/pnas.86.20.8147 2554301
     [Google Scholar]
  65. BakerM.D. ChandraS.Y. DingY. WaxmanS.G. WoodJ.N. GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neurones.J. Physiol.2003548237338210.1113/jphysiol.2003.039131 12651922
     [Google Scholar]
  66. PatlakJ.B. OrtizM. Two modes of gating during late Na+ channel currents in frog sartorius muscle.J. Gen. Physiol.198687230532610.1085/jgp.87.2.305 2419486
     [Google Scholar]
  67. BöhleT. BenndorfK. Multimodal action of single Na+ channels in myocardial mouse cells.Biophys. J.199568112113010.1016/S0006‑3495(95)80166‑9 7711232
     [Google Scholar]
  68. BakerM.D. BostockH. Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture.J. Neurophysiol.19977731503151310.1152/jn.1997.77.3.1503 9084615
     [Google Scholar]
  69. AlzheimerC. SchwindtP.C. CrillW.E. Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex.J. Neurosci.199313266067310.1523/JNEUROSCI.13‑02‑00660.1993 8381170
     [Google Scholar]
  70. SchwindtP.C. CrillW.E. Amplification of synaptic current by persistent sodium conductance in apical dendrite of neocortical neurons.J. Neurophysiol.19957452220222410.1152/jn.1995.74.5.2220 8592214
     [Google Scholar]
  71. RamanI.M. BeanB.P. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.J. Neurosci.199717124517452610.1523/JNEUROSCI.17‑12‑04517.1997 9169512
     [Google Scholar]
  72. MeislerM.H. PlummerN.W. BurgessD.L. BuchnerD.A. SprungerL.K. Allelic mutations of the sodium channel SCN8A reveal multiple cellular and physiological functions.Genetica20041221374510.1007/s10709‑004‑1441‑9 15619959
     [Google Scholar]
  73. MeislerM.H. KearneyJ.A. Sodium channel mutations in epilepsy and other neurological disorders.J. Clin. Invest.200511582010201710.1172/JCI25466 16075041
     [Google Scholar]
  74. LamplI. SchwindtP. CrillW. Reduction of cortical pyramidal neuron excitability by the action of phenytoin on persistent Na+ current.J. Pharmacol. Exp. Ther.19982841228237 9435183
     [Google Scholar]
  75. CumminsT.R. Dib-HajjS.D. HerzogR.I. WaxmanS.G. Na v 1.6 channels generate resurgent sodium currents in spinal sensory neurons.FEBS Lett.2005579102166217010.1016/j.febslet.2005.03.009 15811336
     [Google Scholar]
  76. GriecoT.M. MalhotraJ.D. ChenC. IsomL.L. RamanI.M. Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current.Neuron200545223324410.1016/j.neuron.2004.12.035 15664175
     [Google Scholar]
  77. BantJ.S. RamanI.M. Control of transient, resurgent, and persistent current by open-channel block by Na channel β4 in cultured cerebellar granule neurons.Proc. Natl. Acad. Sci. USA201010727123571236210.1073/pnas.1005633107 20566860
     [Google Scholar]
  78. JareckiB.W. PiekarzA.D. JacksonJ.O.II CumminsT.R. Human voltage-gated sodium channel mutations that cause inherited neuronal and muscle channelopathies increase resurgent sodium currents.J. Clin. Invest.2010120136937810.1172/JCI40801 20038812
     [Google Scholar]
  79. YuF.H. MantegazzaM. WestenbroekR.E. RobbinsC.A. KalumeF. BurtonK.A. SpainW.J. McKnightG.S. ScheuerT. CatterallW.A. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.Nat. Neurosci.2006991142114910.1038/nn1754 16921370
     [Google Scholar]
  80. MeislerM.H. O’BrienJ.E. SharkeyL.M. Sodium channel gene family: Epilepsy mutations, gene interactions and modifier effects.J. Physiol.2010588111841184810.1113/jphysiol.2010.188482 20351042
     [Google Scholar]
  81. CossetteP. LoukasA. LafrenièreR.G. RochefortD. Harvey-GirardE. RagsdaleD.S. DunnR.J. RouleauG.A. Functional characterization of the D188V mutation in neuronal voltage-gated sodium channel causing generalized epilepsy with febrile seizures plus (GEFS).Epilepsy Res.2003531-210711710.1016/S0920‑1211(02)00259‑0 12576172
     [Google Scholar]
  82. SpampanatoJ. EscaygA. MeislerM.H. GoldinA.L. Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2.J. Neurosci.200121197481749010.1523/JNEUROSCI.21‑19‑07481.2001 11567038
     [Google Scholar]
  83. RagsdaleD.S. How do mutant Nav1.1 sodium channels cause epilepsy?Brain Res. Brain Res. Rev.200858114915910.1016/j.brainresrev.2008.01.003 18342948
     [Google Scholar]
  84. SijbenA.E.J. SithinamsuwanP. RadhakrishnanA. BadawyR.A.B. DibbensL. MazaribA. LevD. Lerman-SagieT. StraussbergR. BerkovicS.F. SchefferI.E. Does a SCN1A gene mutation confer earlier age of onset of febrile seizures in GEFS+?Epilepsia200950495395610.1111/j.1528‑1167.2009.02023.x 19292758
     [Google Scholar]
  85. GuerriniR. DravetC. GentonP. BelmonteA. KaminskaA. DulacO. Lamotrigine and seizure aggravation in severe myoclonic epilepsy.Epilepsia199839550851210.1111/j.1528‑1157.1998.tb01413.x 9596203
     [Google Scholar]
  86. WestenbroekR.E. MerrickD.K. CatterallW.A. Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons.Neuron19893669570410.1016/0896‑6273(89)90238‑9 2561976
     [Google Scholar]
  87. BoikoT. RasbandM.N. LevinsonS.R. CaldwellJ.H. MandelG. TrimmerJ.S. MatthewsG. Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon.Neuron20013019110410.1016/S0896‑6273(01)00265‑3 11343647
     [Google Scholar]
  88. KaplanM.R. ChoM.H. UllianE.M. IsomL.L. LevinsonS.R. BarresB.A. Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier.Neuron200130110511910.1016/S0896‑6273(01)00266‑5 11343648
     [Google Scholar]
  89. Planells-CasesR. CapriniM. ZhangJ. RockensteinE.M. RiveraR.R. MurreC. MasliahE. MontalM. Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice.Biophys. J.20007862878289110.1016/S0006‑3495(00)76829‑9 10827969
     [Google Scholar]
  90. HeronS.E. CrosslandK.M. AndermannE. PhillipsH.A. HallA.J. BleaselA. ShevellM. MerchoS. SeniM.H. GuiotM.C. MulleyJ.C. BerkovicS.F. SchefferI.E. Sodium-channel defects in benign familial neonatal-infantile seizures.Lancet2002360933685185210.1016/S0140‑6736(02)09968‑3 12243921
     [Google Scholar]
  91. MisraS.N. KahligK.M. GeorgeA.L.Jr Impaired Na V 1.2 function and reduced cell surface expression in benign familial neonatal‐infantile seizures.Epilepsia20084991535154510.1111/j.1528‑1167.2008.01619.x 18479388
     [Google Scholar]
  92. WhitakerW.R.J. FaullR.L.M. WaldvogelH.J. PlumptonC.J. EmsonP.C. ClareJ.J. Comparative distribution of voltage-gated sodium channel proteins in human brain.Brain Res. Mol. Brain Res.2001881-2375310.1016/S0169‑328X(00)00289‑8 11295230
     [Google Scholar]
  93. HollandK.D. KearneyJ.A. GlauserT.A. BuckG. KeddacheM. BlankstonJ.R. GlaaserI.W. KassR.S. MeislerM.H. Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy.Neurosci. Lett.20084331657010.1016/j.neulet.2007.12.064 18242854
     [Google Scholar]
  94. EstacionM. GasserA. Dib-HajjS.D. WaxmanS.G. A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons.Exp. Neurol.2010224236236810.1016/j.expneurol.2010.04.012 20420834
     [Google Scholar]
  95. WaxmanS.G. KocsisJ.D. BlackJ.A. Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is reexpressed following axotomy.J. Neurophysiol.199472146647010.1152/jn.1994.72.1.466 7965028
     [Google Scholar]
  96. Dib-HajjS.D. FjellJ. CumminsT.R. ZhengZ. FriedK. LaMotteR. BlackJ.A. WaxmanS.G. Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain.Pain199983359160010.1016/S0304‑3959(99)00169‑4 10568868
     [Google Scholar]
  97. PatinoG.A. IsomL.L. Electrophysiology and beyond: Multiple roles of Na+ channel β subunits in development and disease.Neurosci. Lett.20104862535910.1016/j.neulet.2010.06.050 20600605
     [Google Scholar]
  98. ZhaoJ. O’LearyM.E. ChahineM. Regulation of Na v 1.6 and Na v 1.8 peripheral nerve Na + channels by auxiliary β-subunits.J. Neurophysiol.2011106260861910.1152/jn.00107.2011 21562192
     [Google Scholar]
  99. SchefferI.E. HarkinL.A. GrintonB.E. DibbensL.M. TurnerS.J. ZielinskiM.A. XuR. JacksonG. AdamsJ. ConnellanM. PetrouS. WellardR.M. BriellmannR.S. WallaceR.H. MulleyJ.C. BerkovicS.F. Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations.Brain2006130110010910.1093/brain/awl272 17020904
     [Google Scholar]
  100. WimmerV.C. ReidC.A. MitchellS. RichardsK.L. ScafB.B. LeawB.T. HillE.L. RoyeckM. HorstmannM.T. CromerB.A. DaviesP.J. XuR. LercheH. BerkovicS.F. BeckH. PetrouS. Axon initial segment dysfunction in a mouse model of genetic epilepsy with febrile seizures plus.J. Clin. Invest.201012082661267110.1172/JCI42219 20628201
     [Google Scholar]
  101. PatinoG.A. BrackenburyW.J. BaoY. Lopez-SantiagoL.F. O’MalleyH.A. ChenC. CalhounJ.D. LafrenièreR.G. CossetteP. RouleauG.A. IsomL.L. Voltage-gated Na+ channel β1B: A secreted cell adhesion molecule involved in human epilepsy.J. Neurosci.20113141145771459110.1523/JNEUROSCI.0361‑11.2011 21994374
     [Google Scholar]
  102. MarchP.A. Seizures: Classification, etiologies, and pathophysiology.Clin. Tech. Small Anim. Pract.199813311913110.1016/S1096‑2867(98)80033‑9 9775502
     [Google Scholar]
  103. PodellM. Epilepsy and seizure classification: A lesson from Leonardo.J. Vet. Intern. Med.19991313410.1111/j.1939‑1676.1999.tb02157.x 10052056
     [Google Scholar]
  104. ZulianiV. FantiniM. RivaraM. Sodium channel blockers as therapeutic target for treating epilepsy: Recent updates.Curr. Top. Med. Chem.201212996297010.2174/156802612800229206 22352864
     [Google Scholar]
  105. EaholtzG. ScheuerT. CatterallW.A. Restoration of inactivation and block of open sodium channels by an inactivation gate peptide.Neuron19941251041104810.1016/0896‑6273(94)90312‑3 8185942
     [Google Scholar]
  106. EaholtzG. ZagottaW.N. CatterallW.A. Kinetic analysis of block of open sodium channels by a peptide containing the isoleucine, phenylalanine, and methionine (IFM) motif from the inactivation gate.J. Gen. Physiol.19981111758210.1085/jgp.111.1.75 9417136
     [Google Scholar]
  107. BailleuxV. ValléeL. NuytsJ.P. HamoirG. PoupaertJ.H. StablesJ.P. VamecqJ. Comparative anticonvulsant activity and neurotoxicity of 4-amino-N-(2,6-dimethylphenyl)phthalimide and prototype antiepileptic drugs in mice and rats.Epilepsia199536655956510.1111/j.1528‑1157.1995.tb02567.x 7555967
     [Google Scholar]
/content/journals/cbc/10.2174/0115734072306875241118105536
Loading
Antiepileptic Impact of Isoindole-1,3-diones Compounds: An Updated Review on Diversified Synthesis and Modes of Action
Curr. Bioact. Compd. 21, E15734072306875 (2025); https://doi.org/10.2174/0115734072306875241118105536
/content/journals/cbc/10.2174/0115734072306875241118105536
/content/journals/cbc/10.2174/0115734072306875241118105536
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Anticonvulsant; antiepileptic drug design; epilepsy; GABA-AT; isoindole-1,3-diones; maximal electroshock seizure

Most Cited Most Cited RSS feed

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