Novel effect of nefopam preventing cGMP increase, oxygen radical formation and neuronal death induced by veratridine

M. Teresa Fernández-Sánchez, Ramón Díaz-Trelles, Antonio Groppetti, Barbara Manfredi, Anna T. Brini, Gabriele Biella, Maria Luisa Sotgiu, Antonello Novelli

Research output: Contribution to journalArticlepeer-review


Nefopam hydrochloride is a potent analgesic compound that possesses a profile distinct from that of opiods or anti-inflammatory drugs. Previous evidence suggested a central action of nefopam but the detailed mechanisms remain unclear. Here we have used cultured cerebellar neurons to test the hypothesis that nefopam may modulate voltage sensitive sodium channel (VSSC) activity. Nefopam (100 μM) effectively prevented NMDA receptor-mediated early appearance (30 min) of toxicity signs induced by the VSSC activator veratridine. Delayed neurotoxicity by veratridine occurring independently from NMDA receptor activation, was also prevented by nefopam. In contrast, excitotoxicity following direct exposure of neurons to glutamate was not affected. Neuroprotection by nefopam was dose-dependent. 50% protection was obtained at 57 μM while full neuroprotection was achieved at 75 μM nefopam. Veratridine-induced sodium influx was completely abolished in nefopam-treated neurons. Intracellular cGMP and oxygen radical formation following VSSC stimulation by veratridine were also effectively prevented by nefopam. Our data are consistent with an inhibitory action of nefopam on VSSC and suggest that nefopam may modulate the release of endogenous glutamate following activation of these channels. This novel action of nefopam may be of great interest for the treatment of neurodegenerative disorders involving excessive glutamate release and neurotransmission.

Original languageEnglish
Pages (from-to)935-942
Number of pages8
Issue number8
Publication statusPublished - 2001


  • Cultured cerebellar neurons
  • Excitotoxicity
  • Glutamate release
  • Nefopam
  • Reactive oxygen species
  • Sodium channels

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology


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