Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons

Luigi Caputi, Atticus Hainsworth, Ezia Guatteo, Alessandro Tozzi, Alessandro Stefani, Francesca Spadoni, Michael Leach, Giorgio Bernardi, Nicola B. Mercuri

Research output: Contribution to journalArticlepeer-review


Excessive glutamatergic activity is implicated in Parkinson's disease (PD) and sodium channel blockade, resulting in inhibition of glutamate release, is a potential therapeutic approach to PD therapy. Beneficial effects of riluzole and lamotrigine have been reported in animal models of PD, but these compounds have relatively low potency as sodium channel inhibitors and also inhibit N and P/Q-type calcium channels. 202W92, a structural analog of lamotrigine, is a potent sodium channel inhibitor, with no effect on N, P/Q-type channels. Here we present the effects of 202W92 on single patch-clamped dopaminergic neurons. 202W92 (≥10 μM) inhibited spontaneous action potential firing and reduced amplitude and frequency of evoked action potentials. It also inhibited the frequency of 4-aminopyridine (4-AP)- and electrically evoked excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs), with >80% inhibition at 10 μM (IC 50 1.5 μM). EPSC and IPSC amplitudes were partially inhibited. 202W92 did not affect postsynaptic responses to locally applied glutamate and GABA, nor spontaneously occurring mini-IPSCs. These actions of 202W92 are compatible with sodium channel inhibition and depression of transmitter release.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
Issue number3
Publication statusPublished - Jun 1 2003


  • Firing discharge
  • Neuroprotection
  • Parkinson's disease
  • Sodium influx
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology


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