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Cited by 247Epilepsy research and treatmentNeuroscience and Neuropharmacology ResearchIon channel regulation and function

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Update on the Mechanism of Action of Antiepileptic Drugs

Meldrum, Brian S.·1996·Epilepsia
DOI 10.1111/j.1528-1157.1996.tb06038.x
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Abstract

Novel antiepileptic drugs (AEDs) are thought to act on voltage-sensitive ion channels, on inhibitory neurotransmission or on excitatory neurotransmission. Two successful examples of rational AED design that potentiate GABA-mediated inhibition are vigabatrin (VGB) by irreversible inhibition of GABA-transaminase, and tiagabine (TGB) by blocking GABA uptake. Lamotrigine (LTG) prolongs inactivation of voltage-dependent sodium channels. The anticonvulsant action of remacemide (RCM) is probably largely due to blockade of NMDA receptors and prolonged inactivation of sodium channels induced by its desglycinated metabolite. Felbamate (FBM) apparently blocks NMDA receptors, potentiates GABA-mediated responses, blocks L-type calcium channels, and possibly also prolongs sodium channel inactivation. Similarly, topiramate (TPM) has multiple probable sites of action, including sodium channels, GABA receptors, and glutamate (AMPA) receptors. Gabapentin (GBP) apparently has a completely novel type of action, probably involving potentiation of GABA-mediated inhibition and possibly also inactivation of sodium channels. The therapeutic advantages of the novel AEDs are as yet only partially explained by our present understanding of their mechanisms of action.

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  • Bupropion is a dual dopamine and norepinephrine reuptake inhibitor FDA-approved for MDD, seasonal affective disorder, and smoking cessation.

    “Bupropion is a dual dopamine and norepinephrine reuptake inhibitor that is FDA-approved for the treatment of major depressive disorder (MDD), seasonal affective disorder, and smoking cessation.106”

    From The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder (2024) · cites this paper as [106]

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Metadata

Authors
Meldrum, B. S.
Affiliations
University of London (GB)
Corresponding author
Meldrum, Brian S.
Venue
Epilepsia
Publisher
Wiley
Published
1996-12
Volume
37
Issue
s6
Pages
S4-11
ISSN
  • 0013-9580 (ISSN-L)
  • 1528-1167
DOI
10.1111/j.1528-1157.1996.tb06038.x
OpenAlex
W2051154442
Cited by
247
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 7 · 2012: 2
FWCI
4.02
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3991 d)
Locations
  • Epilepsia (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
antiepileptic drugs, mechanism of action, voltage-gated ion channels, sodium channel inactivation, GABAergic inhibition, GABA transaminase inhibition, vigabatrin, tiagabine, lamotrigine, remacemide, felbamate, topiramate, gabapentin, NMDA receptor blockade, L-type calcium channel blockade, AMPA receptors, rational drug design
MeSH terms
Gabapentin, Lamotrigine, Topiramate, Tiagabine, Felbamate, Acetamides, Acetates, Amines, 4-Aminobutyrate Transaminase, Animals, Anticonvulsants, Cyclohexanecarboxylic Acids, Epilepsy, Fructose, gamma-Aminobutyric Acid, Humans, Ion Channels, Membrane Potentials, Synaptic Transmission, Nipecotic Acids, Phenethylamines, Propylene Glycols, Triazines, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA, Neurotransmitter Agents, Vigabatrin, Phenylcarbamates, Mice, Rats

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