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

被引:31
作者
Fernández-Sánchez, MT
Díaz-Trelles, R
Groppetti, A
Manfredi, B
Brini, AT
Biella, G
Sotgiu, ML
Novelli, A
机构
[1] Univ Oviedo, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain
[2] Univ Oviedo, Dept Psychol, E-33006 Oviedo, Spain
[3] Univ Milan, Dept Pharmacol Chemotherapy & Med Toxicol, I-20122 Milan, Italy
[4] Univ Milan, Dept Sci & Biomed Technol, I-20122 Milan, Italy
[5] CNR, Inst Neurosci & Bioimaging, Segrate, Italy
关键词
excitotoxicity; NMDA receptor antagonist; voltage sensitive sodium channels; cerebellar neurons in culture;
D O I
10.1007/s00726-001-0106-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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,muM) 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.
引用
收藏
页码:31 / 36
页数:6
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