Nefopam is more potent than carbamazepine for neuroprotection against veratridine in vitro and has anticonvulsant properties against both electrical and chemical stimulation

• Published in: Amino acids 2007-04, Vol.32 (3), p.323-332
• Main Authors: Novelli, A, Groppetti, A, Rossoni, G, Manfredi, B, Ferrero-Gutiérrez, A, Pérez-Gómez, A, Desogus, C. M, Fernández-Sánchez, M. T
• Format: Article
• Language: English
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; Anticonvulsants - pharmacology; Antitubercular Agents - toxicity; behavior; Calcium; Calcium Channels, L-Type; Calcium Signaling - drug effects; Carbamazepine; Carbamazepine - pharmacology; Cells, Cultured; Cerebellum - metabolism; Cerebellum - pathology; Cultured cerebellar neurons; Dose-Response Relationship, Drug; Electroshock - adverse effects; Glutamic Acid - pharmacology; Isoniazid - toxicity; Male; Mice; Nefopam; Nefopam - pharmacology; Neurodegeneration; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; seizures; Seizures - chemically induced; Seizures - metabolism; Seizures - pathology; Seizures - prevention & control; Veratridine - toxicity
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-006-0419-6

Nefopam (NEF) is a known analgesic that has recently been shown to be effective in controlling both neuropathic pain and convulsions in rodents. In this study we compared nefopam to carbamazepine (CBZ), a reference antiepileptic drug (AED), for their ability to protect cerebellar neuronal cultures from neurodegeneration induced by veratridine (VTD). Furthermore, we tested nefopam for protection against both, maximal electroshock-induced seizures (MES), and isoniazid-induced seizures in mice. Both NEF and CBZ were effective in preventing both signs of excitotoxicity and neurodegeneration following exposure of cultures to 5 μM veratridine for 30 min and 24 h, respectively. Concentrations providing full neuroprotection were 500 μM CBZ and 50 μM NEF, while the concentration providing 50% neuroprotection was 200 μM for CBZ and 20 μM for NEF. Neither NEF nor CBZ reduced excitotoxicity following direct exposure of cultures to glutamate, but CBZ failed to reduce increases in intracellular calcium following stimulation of L-type voltage sensitive calcium channels. In vivo, NEF (20 mg/kg i.p.) significantly reduced MES and fully prevented MES-induced terminal clonus (TC). In comparison, NEF was significantly more effective than CBZ in preventing MES, although both drugs were equally effective against MES-induced TC. Furthermore, nefopam provided protection against isoniazid-induced seizures at doses similar to those protecting against MES.