Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy

Shampa Ghosh; Jitendra Kumar Sinha; Tarab Khan; Kuramkote Shivanna Devaraju; Prabhakar Singh; Kumar Vaibhav; Pankaj Gaur

doi:10.3390/biomedicines9050470

journal article Open Access Apr 25, 2021

Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy

Shampa Ghosh

Jitendra Kumar Sinha

Tarab Khan Kuramkote Shivanna Devaraju Prabhakar Singh

Kumar Vaibhav

Pankaj Gaur

Biomedicines Vol. 9 No. 5 pp. 470 · MDPI AG

View at Publisher Save 10.3390/biomedicines9050470

Abstract

Epilepsy affects around 50 million people across the globe and is the third most common chronic brain disorder. It is a non-communicable disease of the brain that affects people of all ages. It is accompanied by depression, anxiety, and substantially increased morbidity and mortality. A large number of third-generation anti-epileptic drugs are available, but they have multiple side-effects causing a decline in the quality of life. The inheritance and etiology of epilepsy are complex with multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play intricate functions to maintain the normal physiology of various neurons. If there is any dysregulation of neurotransmission due to aberrant transmitter levels or their receptor biology, it can result in seizures. In this review, we have discussed the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Drug-resistant epilepsy (DRE) has remained one of the forefront areas of epilepsy research for a long time. Understanding the mechanisms underlying DRE is of utmost importance because of its high incidence rate among epilepsy patients and increased risks of psychosocial problems and premature death. Here we have enumerated various hypotheses of DRE. Further, we have discussed different non-conventional therapeutic strategies, including combination therapy and non-drug treatment. The recent studies supporting the modern approaches for the treatment of epilepsy have been deliberated with particular reference to the mTOR pathway, breakdown of the blood-brain barrier, and inflammatory pathways.

Topics

No keywords indexed for this article. Browse by subject →

References

83

[1]

Scharfman "The neurobiology of epilepsy" Curr. Neurol. Neurosci. Rep. (2007) 10.1007/s11910-007-0053-z

[2]

Kobylarek "Advances in the Potential Biomarkers of Epilepsy" Front. Neurol. (2019) 10.3389/fneur.2019.00685

[3]

ILAE Official Report: A practical clinical definition of epilepsy

Robert S. Fisher, Carlos Acevedo, Alexis Arzimanoglou et al.

Epilepsia 2014 10.1111/epi.12550

[4]

Schmidt "Evidence-based review on the natural history of the epilepsies" Curr. Opin. Neurol. (2012) 10.1097/wco.0b013e3283507e73

[5]

Berg "Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009" Epilepsia (2010) 10.1111/j.1528-1167.2010.02522.x

[6]

Klitgaard "New avenues for anti-epileptic drug discovery and development" Nat. Rev. Drug Discov. (2013) 10.1038/nrd4126

[7]

Schmidt "Is antiepileptogenesis a realistic goal in clinical trials? Concerns and new horizons" Epileptic Disord (2012) 10.1684/epd.2012.0512

[8]

Brodie "Patterns of treatment response in newly diagnosed epilepsy" Neurology (2012) 10.1212/wnl.0b013e3182563b19

[9]

Mishra "Cognition and memory impairment attenuation via reduction of oxidative stress in acute and chronic mice models of epilepsy using antiepileptogenic Nux vomica" J. Ethnopharmacol. (2021) 10.1016/j.jep.2020.113509

[10]

Wang "Epilepsy-associated genes" Seizure (2017) 10.1016/j.seizure.2016.11.030

[11]

Chaves "Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: A three microRNA panel" Eur. J. Neurol. (2020) 10.1111/ene.14129

[12]

Caramaschi "Epigenome-wide association study of seizures in childhood and adolescence" Clin. Epigenet. (2020) 10.1186/s13148-019-0793-z

[13]

Dedic "A nonsense mutation in FMR1 causing fragile X syndrome" Eur. J. Hum. Genet. (2011) 10.1038/ejhg.2010.223

[14]

Lipinski "Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus" Nat. Neurosci. (2019) 10.1038/s41593-019-0476-2

[15]

Pederick "Abnormal Cell Sorting Underlies the Unique X-Linked Inheritance of PCDH19 Epilepsy" Neuron (2018) 10.1016/j.neuron.2017.12.005

[16]

Lefebvre "Protocadherins mediate dendritic self-avoidance in the mammalian nervous system" Nat. Cell Biol. (2012)

[17]

Toth "Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain" Annu. Rev. Pharmacol. Toxicol. (2021) 10.1146/annurev-pharmtox-030220-022920

[18]

Eboison "The Biochemistry and Epigenetics of Epilepsy: Focus on Adenosine and Glycine" Front. Mol. Neurosci. (2016)

[19]

Kobow "The emerging role of DNA methylation in epileptogenesis" Epilepsia (2012) 10.1111/epi.12031

[20]

Symonds "CHD2 epilepsy: Epigenetics and the quest for precision medicine" Dev. Med. Child Neurol. (2019) 10.1111/dmcn.14380

[21]

Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons

Jian Feng, Yu Zhou, Susan L Campbell et al.

Nature Neuroscience 2010 10.1038/nn.2514

[22]

Henshall "Epigenetics and Epilepsy" Cold Spring Harb. Perspect. Med. (2015) 10.1101/cshperspect.a022731

[23]

Choe "DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures" Clin. Epigenetics (2019) 10.1186/s13148-019-0721-2

[24]

Boison "Epigenetics and epilepsy prevention: The therapeutic potential of adenosine and metabolic therapies" Neuropharmacol. (2020) 10.1016/j.neuropharm.2019.107741

[25]

Epigenetic interventions for epileptogenesis: A new frontier for curing epilepsy

Iyan Younus, Doodipala Samba Reddy

Pharmacology & Therapeutics 2017 10.1016/j.pharmthera.2017.03.002

[26]

Boison "Adenosine Kinase: Exploitation for Therapeutic Gain" Pharmacol. Rev. (2013) 10.1124/pr.112.006361

[27]

Longo, R., Peri, C., Cricrì, D., Coppi, L., Caruso, D., Mitro, N., De Fabiani, E., and Crestani, M. (2019). Ketogenic Diet: A New Light Shining on Old but Gold Biochemistry. Nutrients, 11. 10.3390/nu11102497

[28]

Jago "Epigenetic Therapeutic Intervention for a Rare Epilepsy Disorder" Epilepsy Curr. (2020) 10.1177/1535759720904162

[29]

Chapman "Glutamate and Epilepsy" J. Nutr. (2000) 10.1093/jn/130.4.1043s

[30]

Salpietro "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders" Nat. Commun. (2019) 10.1038/s41467-019-10910-w

[31]

Kumar "A Developmental Switch of AMPA Receptor Subunits in Neocortical Pyramidal Neurons" J. Neurosci. (2002) 10.1523/jneurosci.22-08-03005.2002

[32]

Meldrum "Glutamate receptors and transporters in genetic and acquired models of epilepsy" Epilepsy Res. (1999) 10.1016/s0920-1211(99)00051-0

[33]

Wang "Double-edged GABAergic synaptic transmission in seizures: The importance of chloride plasticity" Brain Res. (2018) 10.1016/j.brainres.2018.09.008

[34]

GABAergic Mechanisms in Epilepsy

David M. Treiman

Epilepsia 2001 10.1046/j.1528-1157.2001.042suppl.3008.x

[35]

Johnson "“Central” and “peripheral” benzodiazepine receptors: Opposite changes in human epileptogenic tissue" Neurology (1992) 10.1212/wnl.42.4.811

[36]

Grunewald "Effects of vigabatrin on partial seizures and cognitive function" J. Neurol. Neurosurg. Psychiatry (1994) 10.1136/jnnp.57.9.1057

[37]

Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System

John A. Dani, Daniel Bertrand

Annual Review of Pharmacology and Toxicology 2007 10.1146/annurev.pharmtox.47.120505.105214

[38]

Raggenbass "Nicotinic receptors in circuit excitability and epilepsy" J. Neurobiol. (2002) 10.1002/neu.10152

[39]

Ghasemi "Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic disorders: Implication for pharmacological interventions" Rev. Neurosci. (2015) 10.1515/revneuro-2014-0044

[40]

Bertrand "How Mutations in the nAChRs Can Cause ADNFLE Epilepsy" Epilepsia (2002) 10.1046/j.1528-1157.43.s.5.16.x

[41]

Hayashi "Lesions of Acetylcholine Neurons in Refractory Epilepsy" ISRN Neurol. (2012) 10.5402/2012/404263

[42]

Bourin, M. (2021). Mechanisms of Action of Anxiolytics. Psychiatry and Neuroscience Update, Springer Science and Business Media LLC. 10.1007/978-3-030-61721-9_18

[43]

Maia "Serotonin depletion increases seizure susceptibility and worsens neuropathological outcomes in kainate model of epilepsy" Brain Res. Bull. (2017) 10.1016/j.brainresbull.2017.07.009

[44]

Singh "Managing epilepsy-associated depression: Serotonin enhancers or serotonin producers?" Epilepsy Behav. (2017) 10.1016/j.yebeh.2016.10.007

[45]

Krishnakumar "Down-regulation of cerebellar 5-HT2C receptors in pilocarpine-induced epilepsy in rats: Therapeutic role of Bacopa monnieri extract" J. Neurol. Sci. (2009) 10.1016/j.jns.2009.04.032

[46]

Bagdy "Serotonin and epilepsy" J. Neurochem. (2007) 10.1111/j.1471-4159.2006.04277.x

[47]

Drug-Resistant Epilepsy

Patrick Kwan, Steven C. Schachter, Martin J. Brodie

New England Journal of Medicine 2011 10.1056/nejmra1004418

[48]

Mohanraj "Mortality in adults with newly diagnosed and chronic epilepsy: A retrospective comparative study" Lancet Neurol. (2006) 10.1016/s1474-4422(06)70448-3

[49]

Lawn "Injuries due to seizures in persons with epilepsy: A population-based study" Neurology (2004) 10.1212/01.wnl.0000142991.14507.b5

[50]

McCagh "Epilepsy, psychosocial and cognitive functioning" Epilepsy Res. (2009) 10.1016/j.eplepsyres.2009.04.007

Showing 50 of 83 references

Metrics

76

Citations

83

References

Details

Published: Apr 25, 2021
Vol/Issue: 9(5)
Pages: 470
License: View

Authors

S

Shampa Ghosh

ICMR-National Institute of Nutrition (NIN), Tarnaka, Hyderabad 500007, India

J

Jitendra Kumar Sinha

Amity Institute of Neuropsychology and Neurosciences (AINN), Amity University UP, Noida 201303, India

T

Tarab Khan

Amity Institute of Neuropsychology and Neurosciences (AINN), Amity University UP, Noida 201303, India

K

Kuramkote Shivanna Devaraju

Department of Biochemistry, Karnatak University, Dharwad 580003, India

P

Prabhakar Singh

Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India

K

Kumar Vaibhav

Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA

P

Pankaj Gaur

Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA

Cite This Article

Shampa Ghosh, Jitendra Kumar Sinha, Tarab Khan, et al. (2021). Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy. Biomedicines, 9(5), 470. https://doi.org/10.3390/biomedicines9050470

Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy

You May Also Like