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 language | English |
|---|---|
| Pages (from-to) | 31-36 |
| Number of pages | 6 |
| Journal | Amino Acids |
| Volume | 23 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - 2002 |
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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 journal › Article
}
TY - JOUR
T1 - Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity
AU - Fernández-Sánchez, M. T.
AU - Díaz-Trelles, R.
AU - Groppetti, A.
AU - Manfredi, B.
AU - Brini, A. T.
AU - Biella, G.
AU - Sotgiu, M. L.
AU - Novelli, A.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Cerebellar neurons in culture
KW - Excitotoxicity
KW - NMDA receptor antagonist
KW - Voltage sensitive sodium channels
UR - http://www.scopus.com/inward/record.url?scp=0036391951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036391951&partnerID=8YFLogxK
U2 - 10.1007/s00726-001-0106-6
DO - 10.1007/s00726-001-0106-6
M3 - Article
C2 - 12373515
AN - SCOPUS:0036391951
VL - 23
SP - 31
EP - 36
JO - Amino Acids
JF - Amino Acids
SN - 0939-4451
IS - 1-3
ER -