Lamotrigine derivatives and riluzole inhibit INa,P in cortical neurons

Francesca Spadoni, Atticus Henry Hainsworth, Nicola Biagio Mercuri, Luigi Caputi, Giuseppina Martella, Franco Lavaroni, Giorgio Bernardi, Alessandro Stefani

Research output: Contribution to journalArticlepeer-review

Abstract

The persistent, slowly inactivating fraction of the sodium current is involved in key functions in the CNS such as dendritic integration of synaptic inputs and cellular excitability. We have studied whether established anti-epileptic drugs and neuroprotective agents target the persistent sodium current. Two lamotrigine derivatives (sipatrigine and 202W92) and riluzole inhibited the persistent sodium current at low, therapeutic concentrations. In contrast, lamotrigine and the classical antiepileptic agents phenytoin and valproic acid blocked the fast-inactivating sodium channel but failed to affect the persistent fraction. The ability to influence either mode of channel activaty may represent a defining feature of each drug sub-class, changing profoundly their clinical indications. Given the damaging role of a sustained influx of sodium in both pharmaco-resistant seizures or excitotoxic insults, we suggest the utilization of drugs that suppress the persistent conductance.

Original languageEnglish
Pages (from-to)1167-1170
Number of pages4
JournalNeuroReport
Volume13
Issue number9
Publication statusPublished - Jul 2 2002

Keywords

  • Lamotrigine derivatives
  • Neuroprotective agents
  • Pharmacology of sodium channel
  • Riluzole
  • Slowly inactivating sodium current

ASJC Scopus subject areas

  • Neuroscience(all)

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