New molecular targets for antiepileptic drugs

α2 δ, SV2A, and Kv7/KCNQ/M potassium channels

Michael A Rogawski, Carl W. Bazil

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Many currently prescribed antiepileptic drugs (AEDs) act via voltage-gated sodium channels, through effects on γ-aminobutyric acid-mediated inhibition, or via voltage-gated calcium channels. Some newer AEDs do not act via these traditional mechanisms. The molecular targets for several of these nontraditional AEDs have been defined using cellular electrophysiology and molecular approaches. Here, we describe three of these targets: α2δ, auxiliary subunits of voltage-gated calcium channels through which the gabapentinoids gabapentin and pregabalin exert their anticonvulsant and analgesic actions; SV2A, a ubiquitous synaptic vesicle glycoprotein that may prepare vesicles for fusion and serves as the target for levetiracetam and its analog brivaracetam (which is currently in late-stage clinical development); and Kv7/KCNQ/M potassium channels that mediate the M-current, which acts a brake on repetitive firing and burst generation and serves as the target for the investigational AEDs retigabine and ICA-105665. Functionally, all of the new targets modulate neurotransmitter output at synapses, focusing attention on presynaptic terminals as critical sites of action for AEDs.

Original languageEnglish (US)
Pages (from-to)345-352
Number of pages8
JournalCurrent Neurology and Neuroscience Reports
Volume8
Issue number4
DOIs
StatePublished - 2008

Fingerprint

KCNQ Potassium Channels
Anticonvulsants
etiracetam
Calcium Channels
Investigational Drugs
Voltage-Gated Sodium Channels
Aminobutyrates
Synaptic Vesicles
Electrophysiology
Presynaptic Terminals
Synapses
Neurotransmitter Agents
Analgesics
Glycoproteins

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

New molecular targets for antiepileptic drugs : α2 δ, SV2A, and Kv7/KCNQ/M potassium channels. / Rogawski, Michael A; Bazil, Carl W.

In: Current Neurology and Neuroscience Reports, Vol. 8, No. 4, 2008, p. 345-352.

Research output: Contribution to journalArticle

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