Dextromethorphan and dextrorphan as calcium channel antagonists.
Dextromethorphan and dextrorphan, which reduce excitatory amino acid-induced neurotoxicity, decreased K+ depolarization-evoked 45Ca2+ uptake into brain synaptosomes and cultured neural (PC12) cells. Half-maximal inhibition of synaptosomal 45Ca2+ uptake occurred with 48 microM dextromethorphan or 200 microM dextrorphan, which are similar to concentrations associated with protection from excitotoxicity. The ability to decrease Ca2+ flux through N-type (synaptosomal) and L-type (PC12) voltage-gated Ca2+ channels may therefore contribute to the neuroprotective effects of these compounds.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D003915:Dextromethorphan / Q000494:pharmacology*; D003917:Dextrorphan / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007981:Levorphanol / Q000031:analogs & derivatives*; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*
D002121:Calcium Channel Blockers; D007473:Ion Channels; D009019:Morphinans; D003917:Dextrorphan; D007981:Levorphanol; D003915:Dextromethorphan; D011188:Potassium; D002118:Calcium