Re: Cough medicine with unique neurprotective mechanisms

[Guest guest]

thanks Natasa, Isobel

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> DXM and Quinidine combo is also used in MS. ...

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> Neurologist. 2007 Sep;13(5):272-93.

> Dextromethorphan as a potential neuroprotective agent with unique mechanisms

> of action.

> Werling LL et al The Institute for Biomedical Sciences, The

> Washington University Medical Center, Washington, DC, USA.

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> Abstract

> BACKGROUND: Dextromethorphan (DM) is a widely-used antitussive. DM's complex

> central nervous system (CNS) pharmacology became of interest when it was

> discovered to be neuroprotective due to its low-affinity, uncompetitive

> N-methyl-D-aspartate (NMDA) receptor antagonism.

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> REVIEW SUMMARY: Mounting preclinical evidence has proven that DM has

> important neuroprotective properties in various CNS injury models, including

> focal and global ischemia, seizure, and traumatic brain injury paradigms.

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> Many of these protective actions seem functionally related to its

> inhibitory effects on glutamate-induced neurotoxicity via NMDA receptor

> antagonist, sigma-1 receptor agonist, and voltage-gated calcium channel

> antagonist actions. DM's protection of dopamine neurons in parkinsonian

> models may be due to inhibition of neurodegenerative inflammatory responses.

> Clinical findings are limited, with preliminary evidence indicating that DM

> protects against neuronal damage. Negative findings seem to relate to

> attainment of inadequate DM brain concentrations. Small studies have shown

> some promise for treatment of perioperative brain injury, amyotrophic

> lateral sclerosis, and symptoms of methotrexate neurotoxicity. DM

> safety/tolerability trials in stroke, neurosurgery, and amyotrophic lateral

> sclerosis patients demonstrated a favorable safety profile. DM's limited

> clinical benefit is proposed to be associated with its rapid metabolism to

> dextrorphan, which restricts its central bioavailability and therapeutic

> utility. Systemic concentrations of DM can be increased via coadministration

> of low-dose quinidine (Q), which reversibly inhibits its first-pass

> elimination. Potential drug interactions with DM/Q are discussed.

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> CONCLUSIONS: Given the compelling preclinical evidence for neuroprotective

> properties of DM, initial clinical neuroprotective findings, and clinical

> demonstrations that the DM/Q combination is well tolerated, this strategy

> may hold promise for the treatment of various acute and degenerative

> neurologic disorders.

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