IC50: ~80 μM for Na+ and Ca2+ channels
Neurons possess a variety of voltage-operated Ca2+ channels, usually labelled L-, T-, N- and P-type, of which only the L-type channels are potently blocked by synthetic compounds of low molecular weight (e.g., dihydropyridines). Dextromethorphan blocks N-methyl-D-aspartate-induced currents and voltage-operated inward currents in cultured cortical neurons.
In vitro: In various in vitro models, high doses of dextromethorphan appear to have both neuroprotective and neurotoxic properties. The neuroprotective activity of the drug has been reported amongst others by Choi who demonstrated that dextromethorphan and dextrorphan can substantially reduce the neurotoxicity of glutamate in vitro [1].
In vivo: Prince and Feeser demonstrated a protective action of dextromethorphan against cerebral infarction in a rat hypoxia-ischaemia model. Engbar and Chase propose that dextromethorphan might prevent neurotoxicity due to long term exposure to low levels of excitotoxins, as may occur in neurological disorders such as Huntington's disease and Alzheimer's disease [1].
Clinical trials: Neuroprofective properties of dextromethorphan have been demonsrated, and treatment with dextromethorphan has been shown to improve the cerebrovascular and functional consequences of cerebral ischemia [1].
Reference:
[1] Bem JL, Peck R. Dextromethorphan. An overview of safety issues. Drug Saf. 1992 May-Jun;7(3):190-9.
