Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage
Li, G., Cui, G., Tzeng, N.-S., Wei, S.-J., Wang, T., Block M. I., Hong, J.-S.
Neuropharmacology Section, Laboratory of Pharmacology and Chemistry and the National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
FASEB J. 19, 489-496 (2005)

Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease (PD). Progress in the search for effective therapeutic strategies that can halt this degenerative process remains limited. We previously showed that micromolar concentrations of dextromethorphan (DM) a major ingredient of widely used antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through the inhibition of microglial activation. In this study, we report that femto- and micromolar concentrations of DM (both pre- and post-treatment) showed equal efficacy in protecting lipopolysaccharide (LPS)-incuced dopaminergic neuron death in midbrain neuron-glia cultures. Both concentrations of DM decreased LPS-induced release of nitric oxide, tumor necrosis factor-alpha, prostaglandin E2 and superoxide from microglia in comparable degrees. The important role of superoxide was demonstrated by DM's failure to show a neuroprotective effect in neuron-glia cultures from NADPH oxidase-deficient mice. These results suggest that the neuroprotective effect elicited by femtomolar concentrations of DM is mediated through the inhibition of LPS-induced proinflammatory factors, especially superoxide. These finding suggest a novel therapeutic concept of using "ultra-low" drug concentrations for the intervention of inflammation-related neurodegenative diseases.

doi: 10. 1096/fj.04-2555com

I realize that LDN and LDDM are not a cure for PD, and some people like Rick may have some problems taking it, but there are several of us that have achieved what we think are significant benefits in the direction of slowing progression. I do not hesitate to urge my own family members who may be at risk for developing PD to take low-dose dextromethorphan. To me, it is a no-brainer for non-symptomataic but susceptible people, or for someone who is very early in the disease process.

Robert