Dextromethorphan analogs are neuroprotective in vitro and block glutamate-induced excitotoxic calcium signals in neurons.
Consistent with the neuroprotective effects of the non-opioid antitussive dextromethorphan (DM) described in several models of CNS injury, micromolar concentrations of three novel analogs of DM markedly attenuated the injury produced by glutamate in cultured rat cortical neurons. Furthermore, the neuroprotective actions of the DM analogs correlated with their effects to block glutamate-induced excitotoxic calcium signals and were unrelated to metabolism to the phencyclidine (PCP)-like drug dextrorphan (DX). These observations establish a new class of compounds related to DM which, by virtue of their efficacy to protect neurons against a severe glutamate insult, may possess therapeutic potential as treatment modalities for a number of neurodegenerative diseases.
Tortella
F C
FC
Department Neuropharmacology and Molecular Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Klette
K L
KL
DeCoster
M A
MA
Davis
B J
BJ
Newman
A H
AH
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D003915:Dextromethorphan / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D003915:Dextromethorphan; D002118:Calcium