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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalAmino Acids
Volume23
Issue number1-3
DOIs
Publication statusPublished - 2002

Fingerprint

Nefopam
Orphenadrine
Veratridine
N-Methyl-D-Aspartate Receptors
Neurons
Sodium Channel Agonists
GABA Agonists
Muscimol
Dizocilpine Maleate
Opioid Analgesics
Toxicity
Analgesics
Glutamic Acid
Anti-Inflammatory Agents
Chemical activation
Membranes

Keywords

  • Cerebellar neurons in culture
  • Excitotoxicity
  • NMDA receptor antagonist
  • Voltage sensitive sodium channels

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry
  • Endocrinology

Cite this

Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity. / Fernández-Sánchez, M. T.; Díaz-Trelles, R.; Groppetti, A.; Manfredi, B.; Brini, A. T.; Biella, G.; Sotgiu, M. L.; Novelli, A.

In: Amino Acids, Vol. 23, No. 1-3, 2002, p. 31-36.

Research output: Contribution to journalArticle

Fernández-Sánchez, MT, Díaz-Trelles, R, Groppetti, A, Manfredi, B, Brini, AT, Biella, G, Sotgiu, ML & Novelli, A 2002, 'Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity', Amino Acids, vol. 23, no. 1-3, pp. 31-36. https://doi.org/10.1007/s00726-001-0106-6
Fernández-Sánchez, M. T. ; Díaz-Trelles, R. ; Groppetti, A. ; Manfredi, B. ; Brini, A. T. ; Biella, G. ; Sotgiu, M. L. ; Novelli, A. / Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity. In: Amino Acids. 2002 ; Vol. 23, No. 1-3. pp. 31-36.
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