Nefopam inhibits calcium influx, cGMP formation, and NMDA receptor-dependent neurotoxicity following activation of voltage sensitive calcium channels
| Autor: | M. T. Fernández-Sánchez, Antonio Groppetti, Antonello Novelli, Ramón Díaz-Trelles |
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| Rok vydání: | 2004 |
| Předmět: |
Agonist
Nefopam Hydrochloride N-Methylaspartate medicine.drug_class Clinical Biochemistry Neurotoxins Excitotoxicity Pharmacology medicine.disease_cause Biochemistry Neuroprotection Receptors N-Methyl-D-Aspartate Calcium in biology Nefopam medicine Excitatory Amino Acid Agonists Animals Calcium Signaling Cyclic GMP Cells Cultured Neurons Kainic Acid Voltage-dependent calcium channel Dose-Response Relationship Drug Chemistry Organic Chemistry 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester Analgesics Non-Narcotic Rats Calcium Channel Agonists Neuromuscular Depolarizing Agents NMDA receptor Calcium Calcium Channels medicine.drug |
| Zdroj: | Amino acids. 28(2) |
| ISSN: | 0939-4451 |
| Popis: | Nefopam hydrochloride is a potent non sedative benzoxazocine analgesic that possesses a profile distinct from that of anti-inflammatory drugs. Previous evidence suggested a central action of nefopam but the detailed mechanism remains unclear. We have investigated the actions of nefopam on voltage sensitive calcium channels and calcium-mediated pathways. We found that nefopam prevented N-methyl-D-aspartate (NMDA)-mediated excitotoxicity following stimulation of L-type voltage sensitive calcium channels by the specific agonist BayK8644. Nefopam protection was concentration-dependent. 47 muM nefopam provided 50% protection while full neuroprotection was achieved at 100 muM nefopam. Neuroprotection was associated with a 73% reduction in the BayK8644-induced increase in intracellular calcium concentration. Nefopam also inhibited intracellular cGMP formation following BayK8644 in a concentration-dependent manner, 100 muM nefopam providing full inhibition of cGMP synthesis and 58 muM allowing 50% cGMP formation. Nefopam reduced NMDA receptor-mediated cGMP formation resulting from the release of glutamate following activation of channels by BayK8644. Finally, we also showed that nefopam effectively reduced cGMP formation following stimulation of cultures with domoic acid, while not providing neuroprotection against domoic acid. Thus, the novel action of nefopam we report here may be important both for its central analgesic effects and for its potential therapeutic use in neurological and neuropsychiatric disorders involving an excessive glutamate release. |
| Databáze: | OpenAIRE |
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