Amino Acids

, Volume 23, Issue 1, pp 31–36

Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity

  • M. T. Fernández-Sánchez
  • R. Díaz-Trelles
  • A. Groppetti
  • B. Manfredi
  • A. T. Brini
  • G. Biella
  • M. L. Sotgiu
  • A. Novelli

DOI: 10.1007/s00726-001-0106-6

Cite this article as:
Fernández-Sánchez, M., Díaz-Trelles, R., Groppetti, A. et al. Amino Acids (2002) 23: 31. doi:10.1007/s00726-001-0106-6

Summary.

 Nefopam hyghochloride is a potent analgesic compound commercialized in most Western Europe for 20 years, which possesses a profile distinct from that of opioids or anti-inflammatory drugs. Previous evidence suggested a central action of nefopam but the detailed mechanisms remain unclear. While, nefopam structure resembles that of orphenadrine, an uncompetitive NMDA receptor antagonist, here we report that differently from orphenadrine, nefopam (100 μM) failed to protect cultured cerebellar neurons from excitotoxicity following direct exposure of neurons to glutamate. Moreover, nefopam failed to displace MK-801 binding to hippocampal membranes. Nefopam effectively prevented NMDA receptor-mediated early appearance (30 min) of toxicity signs induced by the voltage sensitive sodium channel (VSSC) activator veratridine. The later phase (24 h) of neurotoxicity by veratridine occurring independently from NMDA receptor activation, was also prevented by nefopam. Nefopam effect was not mimicked by the GABA receptor agonist muscimol.

Keywords: ExcitotoxicityNMDA receptor antagonistVoltage sensitive sodium channelsCerebellar neurons in culture

Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • M. T. Fernández-Sánchez
    • 1
  • R. Díaz-Trelles
    • 1
  • A. Groppetti
    • 3
  • B. Manfredi
    • 3
  • A. T. Brini
    • 3
  • G. Biella
    • 4
  • M. L. Sotgiu
    • 5
  • A. Novelli
    • 1
  1. 1. Department of Biochemistry and Molecular Biology, University of Oviedo, Oviedo, SpainES
  2. 2. Department of Psychology, University of Oviedo, Oviedo, SpainES
  3. 3. Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, ItalyIT
  4. 4. Department of Science and Biomedical Technologies, University of Milan, Milan, ItalyIT
  5. 5. Institute of Neuroscience and Bioimaging, CNR, Segrate, ItalyIT