IJDDP/
Articles/
2504000154
  • Open Access
  • Review
Mechanism of Anti-seizure Medications and Emerging Trends in Epilepsy Treatment
  • Zubin Singh Rana 1,   
  • Reena Suman 1,   
  • Shobi Veleri 2,   
  • Pradeep Punnakkal 1, *

Received: 28 Nov 2022 | Accepted: 24 Jan 2023 | Published: 27 Jun 2023

Abstract

About one percent of the world’s population is affected by epilepsy. Epilepsy-induced psychiatric co-morbidity and mortality impose a huge burden on patients, their families, and society. Anti-seizure medications (ASMs) are drugs used to control seizures in patients with epilepsy. Epilepsy constitutes a spectrum of disorders, with various underlying causes. Hence, finding the right drug to control seizures with minimal side effects is a difficult task for clinicians. Besides controlling seizures, many ASMs have off-target effects that result in unwanted side effects. Compared to first and second-generation drugs, third-generation drugs have shown better tolerance. Even though the target of many ASMs is known, their mechanism of action is not well understood. The main mechanism behind epilepsy is defined as an imbalance in the excitatory-to-inhibitory ratio in neurotransmission. So, the key target of ASMs is the ion channels controlling the intrinsic property of neurons like sodium channels, potassium channels, and calcium channels, the excitatory synaptic transmission via glutamate receptors, and the inhibitory synaptic transmission by GABA receptors. Here we review the role of ion channels in epilepsy, and how the ASMs act on them for seizure control.

References 

  • 1.
    Trinka E.; Kwan P.; Lee B.; et al. Epilepsy in Asia: disease burden, management barriers, and challenges. Epilepsia, 2019, 60( S1): 7- 21.
  • 2.
    Banerjee J.; BanerjeeDixit A.; Srivastava A.; et al. Altered glutamatergic tone reveals two distinct resting state networks at the cellular level in hippocampal sclerosis. Sci. Rep., 2017, 7( 1): 319.
  • 3.
    Jafarian M.; Modarres Mousavi S.M.; Alipour F.; et al. Cell injury and receptor expression in the epileptic human amygdala. Neurobiol. Dis., 2019, 124: 416- 427.
  • 4.
    Müller L.; Tokay T.; Porath K.; et al. Enhanced NMDA receptor-dependent LTP in the epileptic CA1 area via upregulation of NR2B. Neurobiol. Dis., 2013, 54: 183- 193.
  • 5.
    Nasarudeen R.; Singh A.; Rana Z.S.; et al. Epileptiform activity induced metaplasticity impairs bidirectional plasticity in the hippocampal CA1 synapses via GluN2B NMDA receptors. Exp. Brain Res., 2022, 240( 12): 3339- 3349.
  • 6.
    Zhang H.P.; Cilz N.I.; Yang C.X.; et al. Depression of neuronal excitability and epileptic activities by group II metabotropic glutamate receptors in the medial entorhinal cortex. Hippocampus, 2015, 25( 11): 1299- 1313.
  • 7.
    Hirsch M.; Hintz M.; Specht A.; et al. Tolerability, efficacy and retention rate of Brivaracetam in patients previously treated with Levetiracetam: a monocenter retrospective outcome analysis. Seizure, 2018, 61: 98- 103.
  • 8.
    Perucca E.; Gram L.; Avanzini G.; et al. Antiepileptic drugs as a cause of worsening seizures. Epilepsia, 1998, 39( 1): 5- 17.
  • 9.
    Kapur J.; Stringer J.L.; Lothman E. W. Evidence that repetitive seizures in the hippocampus cause a lasting reduction of GABAergic inhibition. J. Neurophysiol., 1989, 61( 2): 417- 426.
  • 10.
    Wendling F.; Bartolomei F.; Bellanger J.J.; et al. Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition. Eur. J. Neurosci., 2002, 15( 9): 1499- 1508.
  • 11.
    Danbolt N.C.; Furness D.N.; Zhou Y. Neuronal vs glial glutamate uptake: resolving the conundrum. Neurochem. Int., 2016, 98: 29- 45.
  • 12.
    Wollmuth L. P. Ion permeation in ionotropic glutamate receptors: still dynamic after all these years. Curr. Opin. Physiol., 2018, 2: 36- 41.
  • 13.
    Conn P.J.; Pin J. P. Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol., 1997, 37( 1): 205- 237.
  • 14.
    Reddy D.S.; Kuruba R. Experimental models of status epilepticus and neuronal injury for evaluation of therapeutic interventions. Int. J. Mol. Sci., 2013, 14( 9): 18284- 18318.
  • 15.
    Levite M.; Goldberg H. Autoimmune epilepsy - novel multidisciplinary analysis, discoveries and insights. Front. Immunol., 2022, 12: 762743.
  • 16.
    Bertocchi I.; Eltokhi A.; Rozov A.; et al. Voltage-independent GluN2A-type NMDA receptor Ca 2+ signaling promotes audiogenic seizures, attentional and cognitive deficits in mice . Commun. Biol., 2021, 4( 1): 59.
  • 17.
    Punnakkal P.; Dominic D. NMDA receptor GluN2 subtypes control epileptiform events in the hippocampus. NeuroMol. Med., 2018, 20( 1): 90- 96.
  • 18.
    Banerjee J.; Banerjee Dixit A.; Tripathi M.; et al. Enhanced endogenous activation of NMDA receptors in pyramidal neurons of hippocampal tissues from patients with mesial temporal lobe epilepsy: a mechanism of hyper excitation. Epilepsy Res., 2015, 117: 11- 16.
  • 19.
    Ben-Ari Y. The GABA excitatory/inhibitory developmental sequence: a personal journey. Neuroscience, 2014, 279: 187- 219.
  • 20.
    Wu C.; Sun D.D. GABA receptors in brain development, function, and injury. Metab. Brain Dis., 2015, 30( 2): 367- 379.
  • 21.
    Cossette P.; Rouleau G. A. Mutated GABA A receptor subunits in idiopathic generalized epilepsy. Epilepsia , 2010, 51( s5): 62.
  • 22.
    Homayoun M.; Shafieian R.; Seghatoleslam M.; et al. Protective impact of Rosa damascena against neural damage in a rat model of pentylenetetrazole (PTZ)-induced seizure . Avicenna J. Phytomed., 2020, 10( 6): 574- 583.
  • 23.
    Baraban S.C.; Taylor M.R.; Castro P.A.; et al. Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression. Neuroscience, 2005, 131( 3): 759- 768.
  • 24.
    Jacob T.C.; Moss S.J.; Jurd R. GABA A receptor trafficking and its role in the dynamic modulation of neuronal inhibition . Nat. Rev. Neurosci., 2008, 9( 5): 331- 343.
  • 25.
    Schlanger S.; Shinitzky M.; Yam D. Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia, 2002, 43( 1): 103- 104.
  • 26.
    Marban E.; Yamagishi T.; Tomaselli G.F. Structure and function of voltage-gated sodium channels. J. Physiol., 1998, 508( 3): 647- 657.
  • 27.
    Catterall A. A. Sodium channels, inherited epilepsy, and antiepileptic drugs. Ann. Rev. Pharmacool. Toxicol., 2014, 54: 317- 338.
  • 28.
    Ogata N.; Ohishi Y. Molecular diversity of structure and function of the voltage-gated Na + channels . Jpn. J. Pharmacol., 2002, 88( 4): 365- 377.
  • 29.
    Rho J.M.; Donevan S.D.; Rogawski M. A. Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and γ-aminobutyric acidA receptors. Ann. Neurol., 1994, 35( 2): 229- 234.
  • 30.
    Yu F.H.; Catterall W. A. Overview of the voltage-gated sodium channel family. Genome Biol., 2003, 4( 3): 207.
  • 31.
    Lopez-Santiago L.F.; Brackenbury W.J.; Chen C.L.; et al. Na + channel Scn1b gene regulates dorsal root ganglion nociceptor excitability in vivo . J. Biol. Chem., 2011, 286( 26): 22913- 22923.
  • 32.
    Mantegazza M.; Cestèle S.; Catterall W. A. Sodium channelopathies of skeletal muscle and brain. Physiol. Rev., 2021, 101( 4): 1633- 1689.
  • 33.
    Ertel E.A.; Campbell K.P.; Harpold M.M.; et al. Nomenclature of voltage-gated calcium channels. Neuron, 2000, 25( 3): 533- 535.
  • 34.
    Stanika R.I.; Villanueva I.; Kazanina G.; et al. Comparative impact of voltage-gated calcium channels and NMDA receptors on mitochondria-mediated neuronal injury. J. Neurosci., 2012, 32( 19): 6642- 6650.
  • 35.
    Ertel E.A.; Campbell K.P.; Harpold M.M.; et al. Nomenclature of voltage-gated calcium channels. Neuron, 2000, 25( 3): 533- 535.
  • 36.
    Simms B.A.; Zamponi G. W. Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron, 2014, 82( 1): 24- 45.
  • 37.
    Dolphin A. C. Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology. J. Physiol., 2016, 594( 19): 5369- 5390.
  • 38.
    Kuo M. M. C.; Haynes W.J.; Loukin S.H.; et al. Prokaryotic K+ channels: from crystal structures to diversity. FEMS Microbiol. Rev., 2005, 29( 5): 961- 985.
  • 39.
    Buckingham S.D.; Kidd J.F.; Law R.J.; et al. Structure and function of two-pore-domain K + channels: contributions from genetic model organisms . Trends Pharmacol. Sci., 2005, 26( 7): 361- 367.
  • 40.
    Cooper E.C.; Harrington E.; Jan Y.N.; et al. M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain. J. Neurosci., 2001, 21( 24): 9529- 9540.
  • 41.
    Monaghan M.M.; Trimmer J.S.; Rhodes K. J. Experimental localization of Kv1 family voltage-gated K + channel α and β subunits in rat hippocampal formation. J. Neurosci., 2001, 21( 16): 5973- 5983.
  • 42.
    Wang H.; Kunkel D.D.; Schwartzkroin P.A.; et al. Localization of Kv1. 1 and Kv1. 2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain. J. Neurosci., 1994, 14( 8): 4588- 4599.
  • 43.
    Levite M.; Goldberg H. Autoimmune epilepsy - novel multidisciplinary analysis, discoveries and insights. Front. Immunol., 2022, 12: 762743.
  • 44.
    Antonio L.L.; Anderson M.L.; Angamo E.A.; et al. In vitro seizure like events and changes in ionic concentration. J. Neurosci. Methods, 2016, 260: 33- 44.
  • 45.
    Punnakkal P.; Dominic D. NMDA receptor GluN2 subtypes control epileptiform events in the hippocampus. NeuroMol. Med., 2018, 20( 1): 90- 96.
  • 46.
    Pal D.K.; Pong A.W.; Chung W. K. Genetic evaluation and counseling for epilepsy. Nat. Rev. Neurosci., 2010, 6( 8): 445- 453.
  • 47.
    Wang J.; Lin Z.J.; Liu L.; et al. Epilepsy-associated genes. Seizure, 2017, 44: 11- 20.
  • 48.
    Scheffer I.E.; 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.
  • 49.
    Bien C.G.; Scheffer I. E. Autoantibodies and epilepsy. Epilepsia, 2011, 52( s3): 18- 22.
  • 50.
    Irani S.R.; Michell A.W.; Lang B.; et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann. Neurol., 2011, 69( 5): 892- 900.
  • 51.
    Lai M.Z.; Hughes E.G.; Peng X.Y.; et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann. Neurol., 2009, 65( 4): 424- 434.
  • 52.
    Lancaster E.; Lai M.Z.; Peng X.Y.; et al. Antibodies to the GABA B receptor in limbic encephalitis with seizures: case series and characterisation of the antigen . Lancet Neurol., 2010, 9( 1): 67- 76.
  • 53.
    Ohkawa T.; Satake S.I.; Yokoi N.; et al. Identification and characterization of GABA A receptor autoantibodies in autoimmune encephalitis. J. Neurosci., 2014, 34( 24): 8151- 8163.
  • 54.
    Petit-Pedrol M.; Armangue T.; Peng X.Y.; et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABA A receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies . Lancet Neurol., 2014, 13( 3): 276- 286.
  • 55.
    Spatola M.; Petit-Pedrol M.; Simabukuro M.M.; et al. Investigations in GABA A receptor antibody-associated encephalitis . Neurology, 2017, 88( 11): 1012- 1020.
  • 56.
    Granata T.; Cross H.; Theodore W.; et al. Immune-mediated epilepsies. Epilepsia, 2011, 52( s3): 5- 11.
  • 57.
    Lancaster E.; Dalmau J. Neuronal autoantigens—pathogenesis, associated disorders and antibody testing. Nat. Rev. Neurosci., 2012, 8( 7): 380- 390.
  • 58.
    Scher M. S. Prenatal contributions to epilepsy: lessons from the bedside. Epileptic Disorders, 2003, 5( 2): 77- 91.
  • 59.
    Bromfield E.B.; Cavazos J.E.; Sirven J. I. Chapter 1 Basic mechanisms underlying seizures and epilepsy. Bromfield E.B.; Cavazos J.E.; Sirven J. I. An introduction to epilepsy [Internet]. West Hartford (CT): American Epilepsy Society, 2006: NBK2510.
  • 60.
    Stafstrom C. E. Mechanisms of action of antiepileptic drugs: the search for synergy. Curr. Opin. Neurol., 2010, 23( 2): 157- 163.
  • 61.
    Brodie M. J. Sodium channel blockers in the treatment of epilepsy. CNS Drugs, 2017, 31( 7): 527- 534.
  • 62.
    Jung H.Y. ; Mickus T. ; Spruston N . Prolonged sodium channel inactivation contributes to dendritic action potential attenuation in hippocampal pyramidal neurons. J. Neurosci., 1997, 17( 17): 6639- 6646.
  • 63.
    Meldrum B.S.; Rogawski M. A. Molecular targets for antiepileptic drug development. Neurotherapeutics, 2007, 4( 1): 18- 61.
  • 64.
    Kuo C. C. A common anticonvulsant binding site for phenytoin, carbamazepine, and lamotrigine in neuronal Na+ channels. Mol. Pharmacol., 1998, 54( 4): 712- 721.
  • 65.
    Rogawski M.A.; Löscher W. The neurobiology of antiepileptic drugs. Nat. Rev. Neurosci., 2004, 5( 7): 553- 564.
  • 66.
    White H.S.; Smith M.D.; Wilcox K. S. Mechanisms of action of antiepileptic drugs. Int. Rev. Neurobiol., 2007, 81: 85- 110.
  • 67.
    Errington A.C.; Stöhr T.; Heers C.; et al. The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Mol. Pharmacol., 2008, 73( 1): 157- 169.
  • 68.
    Hebeisen S.; Pires N. ; Loureiro A.I.; et al. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology, 2015, 89: 122- 135.
  • 69.
    Lingamaneni R.; Hemmings H.C., Jr. Effects of anticonvulsants on veratridine- and KCl-evoked glutamate release from rat cortical synaptosomes. Neurosci. Lett., 1999, 276( 2): 127- 130.
  • 70.
    Prakriya M.; Mennerick S. Selective depression of low-release probability excitatory synapses by sodium channel blockers. Neuron, 2000, 26( 3): 671- 682.
  • 71.
    Fink K.; Dooley D.J.; Meder W.P.; et al. Inhibition of neuronal Ca 2+ influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology, 2002, 42( 2): 229- 236.
  • 72.
    Sayer R.J.; Brown A.M.; Schwindt P.C.; et al. Calcium currents in acutely isolated human neocortical neurons. J. Neurophysiol., 1993, 69( 5): 1596- 1606.
  • 73.
    Mula M.; Pini S.; Cassano G. B. The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J. Clin. Psychopharmacol., 2007, 27( 3): 263- 272.
  • 74.
    Stefani A.; Spadoni F.; Siniscalchi A.; et al. Lamotrigine inhibits Ca 2+ currents in cortical neurons: functional implications . Eur. J. Pharmacol., 1996, 307( 1): 113- 116.
  • 75.
    Cooper E.C.; Harrington E.; Jan Y.N.; et al. M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain. J. Neurosci., 2001, 21( 24): 9529- 9540.
  • 76.
    Rogawski M. A. Single voltage-dependent potassium channels in cultured rat hippocampal neurons. J. Neurophysiol., 1986, 56( 2): 481- 493.
  • 77.
    Wickenden A. D. Potassium channels as anti-epileptic drug targets. Neuropharmacology, 2002, 43( 7): 1055- 1060.
  • 78.
    Treiman D. M. GABAergic mechanisms in epilepsy. Epilepsia, 2001, 42( s3): 8- 12.
  • 79.
    Pennell P.B.; Ogaily M.S.; Macdonald R. L. Aplastic anemia in a patient receiving felbamate for complex partial seizures. Neurology, 1995, 45( 3): 456- 460.
  • 80.
    O’Neil M.G.; Perdun C.S.; Wilson M.B.; et al. Felbamate‐associated fatal acute hepatic necrosis. Neurology, 1996, 46( 5): 1457.
  • 81.
    Greenfield L.J., Jr. Molecular mechanisms of antiseizure drug activity at GABA A receptors . Seizure, 2013, 22( 8): 589- 600.
  • 82.
    Han S.; Tai C.; Westenbroek R.E.; et al. Autistic-like behaviour in Scn1a +/ - mice and rescue by enhanced GABA-mediated neurotransmission . Nature, 2012, 489( 7416): 385- 390.
  • 83.
    Minabe Y.; Emori K.; Shibata R.; et al. Antiepileptic effects of MK-801, a noncompetitive NMDA-receptor antagonist, in the low-frequency kindling model of epilepsy. Jpn. J. Psychiatry Neurol., 1992, 46( 3): 755- 761.
  • 84.
    Hasegawa N.; Tohyama J. Positive and negative effects of perampanel treatment on psychiatric and behavioral symptoms in adult patients with epilepsy. Epilepsy & Behavior, 2021, 117: 107515.
  • 85.
    Szoeke C. E.I.; Newton M.; Wood J.M.;et al. Update on pharmacogenetics in epilepsy: a brief review. Lancet Neurol., 2006, 5( 2): 189- 196.
  • 86.
    Löscher W.; Klitgaard H.; Twyman R.E.; et al. New avenues for anti-epileptic drug discovery and development. Nat. Rev. Drug Discov., 2013, 12( 10): 757- 776.
  • 87.
    Dhiman V. Molecular genetics of epilepsy: a clinician’s perspective. Ann. Indian Acad.Neurol., 2017, 20( 2): 96- 102.
  • 88.
    Chuan Z.; Ruikun C.; Qian L.; et al. Genetic and phenotype analysis of a Chinese cohort of infants and children with epilepsy. Front. Genet., 2022, 13: 869210.
  • 89.
    Solazzi R.; Moscatelli M.; Sebastiano D.R.; et al. Severe epilepsy and movement disorder may be early symptoms of TMEM106B-related hypomyelinating leukodystrophy. Neurol. Genet., 2022, 8( 5): e200022.
  • 90.
    Liu J. Y.W.; Reeves C.; Diehl B.; et al. Early lipofuscin accumulation in frontal lobe epilepsy. Ann. Neurol., 2016, 80( 6): 882- 895.
  • 91.
    Wolff M.; Johannesen K.M.; Hedrich U. B.S.; et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain, 2017, 140( 5): 1316- 1336.
  • 92.
    Sawaishi Y.; Yano T.; Enoki M.; et al. Lidocaine-dependent early infantile status epilepticus with highly suppressed EEG. Epilepsia, 2002, 43( 2): 201- 204.
  • 93.
    Johannessen Landmark C.; Johannessen S.I.; Tomson T. Host factors affecting antiepileptic drug delivery-pharmacokinetic variability. Adv. Drug Delivery Rev., 2012, 64( 10): 896- 910.
  • 94.
    Johannessen Landmark C.; Johannessen S.I.; Patsalos P. N. Therapeutic drug monitoring of antiepileptic drugs: current status and future prospects. Expert Opin. Drug Metab. Toxicol., 2020, 16( 3): 227- 238.
  • 95.
    Tomson T.; Landmark C.J.; Battino D. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia, 2013, 54( 3): 405- 414.
  • 96.
    Johannessen Landmark C.; Patsalos P. N. Drug interactions involving the new second- and third-generation antiepileptic drugs. Expert Rev. Neurother., 2010, 10( 1): 119- 140.
  • 97.
    Lopez-Garcia M.A.; Feria-Romero I.A.; Fernando-Serrano H.; et al. Genetic polymorphisms associated with antiepileptic metabolism. Front. Biosci. (Elite Ed), 2014, 6( 2): 377- 386.
  • 98.
    Caudle K.E.; Rettie A.E.; Whirl-Carrillo M.; et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing . Clin. Pharmacol. Ther., 2014, 96( 5): 542- 548.
  • 99.
    Franco V.; Perucca E. CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Expert Opin. Drug Metab. Toxicol., 2015, 11( 8): 1269- 1279.
  • 100.
    Chu X.M.; Zhang L.F.; Wang G.J.; et al. Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients. Eur. J. Clin. Pharmacol., 2012, 68( 10): 1395- 1401.
  • 101.
    Potschka H.; Brodie M. J. Handb Clin neurol. Handb. Clin. Neurol., 2012, 108: 741- 757.
  • 102.
    Tate S.K.; Depondt C.; Sisodiya S.M.; al et. Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc. Natl. Acad. Sci. USA., 2005, 102( 15): 5507- 5512.
  • 103.
    Haerian B.S.; Baum L.; Kwan P.; et al. SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis . Pharmacogenomics, 2013, 14( 10): 1153- 1166.
  • 104.
    Božina N.; Sporiš I.Š.; Božina T.; et al. Pharmacogenetics and the treatment of epilepsy: what do we know? Pharmacogenomics, 2019, 20( 15): 1093- 1101.
  • 105.
    Mirza N.; Vasieva O.; Appleton R.; et al. An integrative in silico system for predicting dysregulated genes in the human epileptic focus: application to SLC transporters . Epilepsia, 2016, 57( 9): 1467- 1474.
  • 106.
    Edwards I.R.; Aronson J. K. Adverse drug reactions: definitions, diagnosis, and management. Lancet, 2000, 356( 9237): 1255- 1259.
  • 107.
    Cramer J.A.; Mintzer S.; Wheless J.; et al. Adverse effects of antiepileptic drugs: a brief overview of important issues. Expert Rev. Neurother., 2010, 10( 6): 885- 891.
  • 108.
    Meador K. J. Cognitive effects of epilepsy and of antiepileptic medications. The treatment of epilepsy: principles and practice. 1996: 1121- 1130.
  • 109.
    Livanainen M.; Savolainen H. Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy. Acta Neurol. Scand., 1983, 68( s97): 49- 67.
  • 110.
    Meador K.J.; Loring D.W.; Hulihan J.F.; et al. Differential cognitive and behavioral effects of topiramate and valproate. Neurology, 2003, 60( 9): 1483- 1488.
  • 111.
    Pellock J. M. Carbamazepine side effects in children and adults. Epilepsia, 1987, 28( s3): S64- S70.
  • 112.
    Keränen T. Sivenius J. Side effects of carbamazepine, valproate and clonazepam during long-term treatment of epilepsy. Acta Neurol. Scand., 1983, 68( s97): 69- 80.
  • 113.
    Dogan E.A.; Usta B.E.; Bilgen R.; et al. Efficacy, tolerability, and side effects of oxcarbazepine monotherapy: a prospective study in adult and elderly patients with newly diagnosed partial epilepsy. Epilepsy & Behavior, 2008, 13( 1): 156- 161.
  • 114.
    Gören M.Z.; Onat F. Ethosuximide: from bench to bedside. CNS Drug Rev., 2007, 13( 2): 224- 239.
  • 115.
    Zaccara G.; Specchio L. M. Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr. Dis. Treat., 2009, 5: 249- 259.
  • 116.
    Li J.Y.; Sun M.Z.; Wang X. F. The adverse-effect profile of lacosamide. Expert Opin. Drug Saf., 2020, 19( 2): 131- 138.
  • 117.
    Bourgeois B. F.D. Felbamate. Semin. Pediatr. Neurol., 1997, 4( 1): 3- 8.
  • 118.
    Lyons J.B.; Liversedge L. A. Primidone in the treatment of epilepsy. Br. Med. J., 1954, 2( 4888): 625- 627.
  • 119.
    Binnie C.D.; van Emde Boas W. ; Kasteleijn-Nolste-Trenite D.G. ; et al . Acute effects of lamotrigine (BW430C) in persons with epilepsy. Epilepsia, 1986, 27( 3): 248- 254.
  • 120.
    Leach J.P.; Brodie M. J. Tiagabine. Lancet, 1998, 351( 9097): 203- 207.
  • 121.
    Hakimian S.; Cheng-Hakimian A.; Anderson G.D.; et al . Rufinamide: a new anti-epileptic medication. Expert Opin. Pharmacother., 2007, 8( 12): 1931- 1940.
  • 122.
    Livingston J.H.; Beaumont D.; Arzimanoglou A.; et al . Vigabatrin in the treatment of epilepsy in children. Br. J. Clin. Pharmacol., 1989, 27( S1): 109S- 112S.
  • 123.
    Almeida L.; Soares-da-Silva P. Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics, 2007, 4( 1): 88- 96.
  • 124.
    Elger C.E.; Helmstaedter C.; Kurthen M . Chronic epilepsy and cognition. Lancet Neurol., 2004, 3( 11): 663- 672.
  • 125.
    Novak A.; Vizjak K.; Rakusa M. Cognitive impairment in people with epilepsy. J. Clin. Med., 2022, 11( 1): 267.
  • 126.
    Hirsch E.; Schmitz B.; Carreño M. Epilepsy, antiepileptic drugs (AEDs) and cognition. Acta Neurol. Scand., 2003, 180( s180): 23- 32.
  • 127.
    Chen B.; Detyniecki K.; Choi H.; et al. Psychiatric and behavioral side effects of anti-epileptic drugs in adolescents and children with epilepsy. Eur. J. Paediatr. Neurol., 2017, 21( 3): 441- 449.
  • 128.
    Mattson R.H.; Cramer J.A.; Collins J.F.; et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N. Engl. J. Med., 1985, 313( 3): 145- 151.
  • 129.
    Smith D.B.; Mattson R.H.; CramerJ.A.; et al. Results of a nationwide Veterans Administration Cooperative Study comparing the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin, and primidone. Epilepsia, 1987, 28( s3): S50- S58.
  • 130.
    Dodrill C.B.; Troupin A. S. Psychotropic effects of carbamazepine in epilepsy: a double-blind comparison with phenytoin. Neurology, 1977, 27( 11): 1023- 1028.
  • 131.
    Trimble M.R.; Thompson P. J. Anticonvulsant drugs, cognitive function, and behavior. Epilepsia, 1983, 24( s1): S55- S63.
  • 132.
    Pulliainen V.; Jokelainen M. Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients. Acta Neurol. Scand., 1994, 89( 2): 81- 86.
  • 133.
    Salinsky M.C.; Spencer D.C.; Oken B.S.; et al. Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers. Epilepsy & Behavior, 2004, 5( 6): 894- 902.
  • 134.
    Shehata G. A. Bateh A. E.A.M.; Hamed S.A.; et al. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate) in adult males with epilepsy. Neuropsychiatr. Dis. Treat., 2009, 5: 527- 533.
  • 135.
    Möhler H.; Rudolph U. Disinhibition, an emerging pharmacology of learning and memory. F1000Research, 2017, 6(F1000 Faculty Rev): 101.
  • 136.
    Drane D.L.; Meador K. J. Cognitive and behavioral effects of antiepileptic drugs. Epilepsy & Behavior, 2002, 3( 5S): 49- 53.
  • 137.
    Jokeit H.; Krämer G.; Ebner A. Do antiepileptic drugs accelerate forgetting? Epilepsy & Behavior, 2005, 6( 3): 430- 432.
  • 138.
    Bonansco C.; Fuenzalida M. Plasticity of hippocampal excitatory-inhibitory balance: missing the synaptic control in the epileptic brain. Neural Plast., 2016, 2016: 8607038.
  • 139.
    Cain D . P. Long-term potentiation and kindling: how similar are the mechanisms? Trends Neurosci., 1989, 12( 1): 6- 10.
  • 140.
    Meador K. J. The basic science of memory as it applies to epilepsy. Epilepsia, 2007, 48( s9): 23- 25.
  • 141.
    Zhang M.M.; Xiao C.; Yu K.; et al. Effects of sodium valproate on synaptic plasticity in the CA1 region of rat hippocampus. Food Chem. Toxicol., 2003, 41( 11): 1617- 1623.
  • 142.
    West P.J.; Saunders G.W.; Remigio G.J.; et al. Antiseizure drugs differentially modulate θ-burst induced long-term potentiation in C57BL/6 mice. Epilepsia, 2014, 55( 2): 214- 223.
  • 143.
    Salaka R.J.; Nair K.P.; Sasibhushana R.B.; et al. Differential effects of levetiracetam on hippocampal CA1 synaptic plasticity and molecular changes in the dentate gyrus in epileptic rats. Neurochem. Int., 2022, 158: 105378.
  • 144.
    Booker S.A.; Pires N.; Cobb S.; et al. Carbamazepine and oxcarbazepine, but not eslicarbazepine, enhance excitatory synaptic transmission onto hippocampal CA1 pyramidal cells through an antagonist action at adenosine A1 receptors. Neuropharmacology, 2015, 93: 103- 115.
  • 145.
    Ge Y.X. ; Lin Y.Y. ; Bi Q.Q. ; et al. Brivaracetam prevents the over-expression of synaptic vesicle protein 2A and rescues the deficits of hippocampal long-term potentiation in vivo in chronic temporal lobe epilepsy rats. Curr. Neurovasc. Res., 2020, 17( 4): 354- 360.
  • 146.
    Heidegger T.; Krakow K.; Ziemann U. Effects of antiepileptic drugs on associative LTP-like plasticity in human motor cortex. Eur. J. Neurosci., 2010, 32( 7): 1215- 1222.
  • 147.
    Ryther R. C.C.; Wong M. Mammalian target of rapamycin (mTOR) inhibition: potential for antiseizure, antiepileptogenic, and epileptostatic therapy. Curr. Neurol. Neurosci. Rep., 2012, 12( 4): 410- 418.
  • 148.
    Vezzani A. Before epilepsy unfolds: finding the epileptogenesis switch. Nat. Med., 2012, 18( 11): 1626- 1627.
  • 149.
    DzhalaV.I.; Talos D.M.; Sdrulla D.A.; et al. NKCC1 transporter facilitates seizures in the developing brain. Nat. Med., 2005, 11( 11): 1205- 1213.
  • 150.
    Soul J.S.; Bergin A.M.; Stopp C.; et al. A pilot randomized, controlled, double-blind trial of bumetanide to treat neonatal seizures. Ann. Neurol., 2021, 89( 2): 327- 340.
  • 151.
    Vezzani A.; Balosso S.; Ravizza T. The role of cytokines in the pathophysiology of epilepsy. Brain, Behav., Immun., 2008, 22( 6): 797- 803.
  • 152.
    Vezzani A.; French J.; Bartfai T.; et al. The role of inflammation in epilepsy. Nat. Rev. Neurol., 2011, 7( 1): 31- 40.
  • 153.
    Librizzi L.; Noè F.; Vezzani A.; et al. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage. Ann. Neurol., 2012, 72( 1): 82- 90.
  • 154.
    Vezzani A.; Moneta D.; Conti M.; et al. Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc. Natl. Acad. Sci. USA., 2000, 97( 21): 11534- 11539.
  • 155.
    Zhang L.; Wang Y. P. Gene therapy in epilepsy . Biomed. Pharmacother., 2021, 143: 112075.
  • 156.
    Gonçalves M. A. Adeno-associated virus: from defective virus to effective vector. Virol. J., 2005, 2( 1): 43.
  • 157.
    Mátrai J.; Chuah M.K.; VandenDriessche T. Recent advances in lentiviral vector development and applications. Mol. Ther., 2010, 18( 3): 477- 490.
  • 158.
    Simonato M.; Manservigi R.; Marconi P.; et al . Gene transfer into neurones for the molecular analysis of behaviour: focus on herpes simplex vectors. Trends Neurosci., 2000, 23( 5): 183- 190.
  • 159.
    Niibori Y.; Lee S.J.; Minassian B.A.; et al. Sexually divergent mortality and partial phenotypic rescue after gene therapy in a mouse model of dravet syndrome. Hum. Gene Ther., 2020, 31( 5/6): 339- 351.
  • 160.
    Qiu Y.C.; O'Neill N.; Maffei B.; et al . On-demand cell-autonomous gene therapy for brain circuit disorders. Science, 2022, 378( 6619): 523- 532.
  • 161.
    Berkovic S.F.; Mulley J.C.; Scheffer I.E.; et al. Human epilepsies: interaction of genetic and acquired factors. Trends Neurosci., 2006, 29( 7): 391- 397.
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10.53941/ijddp.2023.100001
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Volume 2, Issue 2
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Rana, Z. S.; Suman, R.; Veleri, S.; Punnakkal, P. Mechanism of Anti-seizure Medications and Emerging Trends in Epilepsy Treatment. International Journal of Drug Discovery and Pharmacology 2023, 2 (2), 1–16. https://doi.org/10.53941/ijddp.2023.100001.
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Zubin Singh Rana, Reena Suman, Shobi Veleri, Pradeep Punnakkal