sorry for repeat of widely discussed topic on this forum .. I thought worth reviving specially for those who are research inclined:
Dextromethorphan Protects Dopaminergic Neurons against
Inflammation-Mediated Degeneration through Inhibition of
Microglial Activation
YUXIN LIU, LIYA QIN, GUORONG LI, WEI ZHANG, LIJIA AN, BIN LIU, and JAU-SHYONG HONG
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (Y.L.,
L.Q., G.L., W.Z., B.L., J.-S.H.); and Department of Bioengineering, Dalian University of Technology, Dalian, China (L.A.)
Received August 12, 2002; accepted December 09, 2002

http://jpet.aspetjournals.org/cgi/reprint/305/1/212.pdf
ABSTRACT
Inflammation in the brain has increasingly been recognized to
play an important role in the pathogenesis of several neurodegenerative
disorders, including Parkinson’s disease and Alzheimer’s
disease. Inflammation-mediated neurodegeneration involves
activation of the brain’s resident immune cells, the
microglia, which produce proinflammatory and neurotoxic factors,
including cytokines, reactive oxygen intermediates, nitric
oxide, and eicosanoids that impact on neurons to induce neurodegeneration.
Hence, identification of compounds that prevent
microglial activation may be highly desirable in the search
for therapeutic agents for inflammation-mediated neurodegenerative
diseases. In this study, we report that dextromethorphan
(DM), an ingredient widely used in antitussive remedies,
reduced the inflammation-mediated degeneration of dopaminergic
neurons through inhibition of microglial activation. Pretreatment
(30 min) of rat mesencephalic neuron-glia cultures
with DM (1–10
M) reduced, in a dose-dependent manner, the
microglia-mediated degeneration of dopaminergic neurons induced
by lipopolysaccharide (LPS, 10 ng/ml). Significant neuroprotection
by DM was also evident when DM was applied to
cultures up to 60 min after the addition of LPS. The neuroprotective
effect of DM was attributed to inhibition of LPS-stimulated
microglial activation because DM significantly inhibited
the LPS-induced production of tumor necrosis factor-, nitric
oxide, and superoxide free radicals. This conclusion was further
supported by the finding that DM failed to prevent 1-methyl-4-
phenylpyridinium- or -amyloid peptide (1–42)-induced dopaminergic
neurotoxicity in neuron-enriched cultures. In addition,
because LPS did not produce any significant increase in the
release of excitatory amino acids from neuron-glia cultures and
N-methyl-D-aspartate antagonist dizocilpine maleate failed to
afford significant neuroprotection, it is unlikely that the neuroprotective
effect of DM is mediated through N-methyl-D-aspartate
receptors. These results suggest that DM may be a promising
therapeutic agent for the treatment of Parkinson’s
disease.
Degeneration of dopaminergic neurons in the substantia
nigra and dopamine-containing nerve fibers in the striatum
is a pathological hallmark of Parkinson’s disease (PD). The
cause and underlying mechanism responsible for the progressive
neurodegeneration of sporadic PD remain unclear (Olanow
and Tatton, 1999). Inflammation in the brain, characterized
by the activation of microglia and astroglia, has been
closely associated with the pathogenesis of PD, as well as
with several other degenerative neurological disorders, including
Alzheimer’s disease (McGeer et al., 1988; McGeer
and McGeer,