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Dextromethorphan and dextrorphan as calcium channel antagonists.
C L Carpenter1, S S Marks, D L Watson
1Department of Neurology, University of California, San Francisco 94110.
Brain Research
|January 26, 1988
Summary
Dextromethorphan and its metabolite dextrorphan reduce brain cell damage by decreasing calcium ion (Ca2+) influx. This action on voltage-gated calcium channels may explain their neuroprotective properties.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Excitatory amino acid-induced neurotoxicity is a significant concern in neurological disorders.
- Dextromethorphan and dextrorphan are known to mitigate this excitotoxicity.
Purpose of the Study:
- To investigate the mechanism by which dextromethorphan and dextrorphan exert neuroprotection.
- To determine if these compounds affect calcium ion (Ca2+) flux into neural cells.
Main Methods:
- Measured K+ depolarization-evoked 45Ca2+ uptake into rat brain synaptosomes.
- Assessed 45Ca2+ uptake in cultured neural PC12 cells.
Main Results:
- Dextromethorphan and dextrorphan significantly decreased 45Ca2+ uptake in both synaptosomes and PC12 cells.
- Effective concentrations for inhibiting Ca2+ uptake were comparable to those providing excitotoxic protection.
- Inhibition involved N-type (synaptosomal) and L-type (PC12) voltage-gated calcium channels.
Conclusions:
- The reduction of Ca2+ influx through voltage-gated calcium channels is a likely mechanism for the neuroprotective effects of dextromethorphan and dextrorphan.
- These findings elucidate a key cellular action contributing to the therapeutic potential of these compounds.