Editing Dexthromethorphan

[[Information on nutritional supplements people with ALS have been taking]]

[https://en.wikipedia.org/wiki/Dextromethorphan Wikipedia page]

[http://www.neurotransmitter.net/drugmechanisms.html neurotransmitter.net]:
:''Dextromethorphan (DXM) is commonly found in over the counter cough remedies.''

:''The drug's antitussive effects are mediated by sigma-1 and serotonin 5-HT1A receptors; at therapeutically relevant concentrations, DXM is likely to cause the activation of 5-HT1A receptors indirectly via the inhibition of serotonin reuptake.''

:''DXM exhibits relatively high affinity binding activity as a sigma-1 receptor agonist and serotonin reuptake inhibitor. DXM is also a noncompetitive NMDA receptor antagonist. The drug is four times more potent at NR1A/NR2A subunit-containing NMDA receptors than at NR1A/NR2B NMDA receptors. Furthermore, DXM exhibits a higher potency at NR1/NR2C receptors than at NR1/NR2A receptors. The active metabolite of DXM, dextrorphan, is a more potent noncompetitive NMDA antagonist and sigma-1 agonist than DXM. Dextrorphan and DXM also bind with low affinity to sigma-2 receptors. DXM and dextrorphan noncompetitively block alpha3beta4 neuronal nicotinic acetylcholine receptors; other nicotinic receptor subtypes may also be affected by these drugs.'' 


== Effects on ALS ==

Dextromethorphan (DM) is a dextrorotary morphinan and a widely used component of cough medicine.  Relatively high doses of DM in combination with quinidine are used for the treatment of mood disorders for patients with multiple sclerosis (MS). However, at lower doses, morphinans exert anti-inflammatory activities through the inhibition of NOX2-dependent superoxide production in activated microglia. [1]

== Discussion threads on the ALSTDI forum ==

[http://www.alstdi.org/forum/yaf_postst50622_how-much-dextromethorphan-is-too-much.aspx How much dextromethorphan is too much?]

[http://www.alstdi.org/forum/yaf_postst50482_cough-syrup-restores-speech-in-pals-overnight.aspx Cough syrup restores speech in PALS overnight]:
:''Do not use dextromethorphan if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take dextromethorphan before the MAO inhibitor has cleared from your body. ''

[http://www.alstdi.org/forum/yaf_postst50343_nuedexta-trial-for-bulbar-issues-of-swallowing-and-speech.aspx Nuedexta trial for bulbar issues and speech?]

== Where to get it ==


== References ==

[1]
<bibtex>
@article{Chechneva2011,
abstract = {Dextromethorphan (DM) is a dextrorotary morphinan and a widely used component of cough medicine. Relatively high doses of DM in combination with quinidine are used for the treatment of mood disorders for patients with multiple sclerosis (MS). However, at lower doses, morphinans exert anti-inflammatory activities through the inhibition of NOX2-dependent superoxide production in activated microglia. Here we investigated the effects of high (10 mg/kg, i.p., "DM-10") and low (0.1 mg/kg, i.p., "DM-0.1") doses of DM on the development and progression of mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We found no protection by high dose DM treatment. Interestingly, a minor late attenuation by low dose DM treatment was seen in severe EAE that was characterized by a chronic disease course and a massive spinal cord infiltration of CD45(+) cells including T-lymphocytes, macrophages and neutrophils. Furthermore, in a less severe form of EAE, where lower levels of CD4(+) and CD8(+) T-cells, Iba1(+) microglia/macrophages and no significant infiltration of neutrophils were seen in the spinal cord, the treatment with DM-0.1 was remarkably more beneficial. The effect was the most significant at the peak of disease and was associated with an inhibition of NOX2 expression and a decrease in infiltration of monocytes and lymphocytes into the spinal cord. In addition, chronic treatment with low dose DM resulted in decreased demyelination and reduced axonal loss in the lumbar spinal cord. Our study is the first report to show that low dose DM is effective in treating EAE of moderate severity. Our findings reveal that low dose morphinan DM treatment may represent a new promising protective strategy for treating MS.},
author = {Chechneva, Olga V and Mayrhofer, Florian and Daugherty, Daniel J and Pleasure, David E and Hong, Jau-Shyong and Deng, Wenbin},
doi = {10.1016/j.nbd.2011.06.004},
file = {:C$\backslash$:/Users/riku/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Chechneva et al. - 2011 - Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and.pdf:pdf},
issn = {1095-953X},
journal = {Neurobiology of disease},
keywords = {Animals,CD4 Lymphocyte Count,CD8-Positive T-Lymphocytes,CD8-Positive T-Lymphocytes: drug effects,Demyelinating Diseases,Demyelinating Diseases: pathology,Dextromethorphan,Dextromethorphan: administration \& dosage,Dextromethorphan: pharmacology,Dose-Response Relationship, Drug,Encephalomyelitis, Autoimmune, Experimental,Encephalomyelitis, Autoimmune, Experimental: drug ,Encephalomyelitis, Autoimmune, Experimental: enzym,Encephalomyelitis, Autoimmune, Experimental: patho,Excitatory Amino Acid Antagonists,Excitatory Amino Acid Antagonists: administration ,Excitatory Amino Acid Antagonists: pharmacology,Glycoproteins,Glycoproteins: biosynthesis,Immunohistochemistry,Lymphocyte Count,Macrophages,Macrophages: drug effects,Macrophages: immunology,Male,Membrane Glycoproteins,Membrane Glycoproteins: antagonists \& inhibitors,Mice,Mice, Inbred C57BL,Microglia,Microglia: drug effects,Myelin-Oligodendrocyte Glycoprotein,NADPH Oxidase,NADPH Oxidase: antagonists \& inhibitors,Neuroprotective Agents,Neutrophil Infiltration,Neutrophil Infiltration: drug effects,Peptide Fragments,Peptide Fragments: biosynthesis,RNA,RNA: biosynthesis,RNA: isolation \& purification,Reverse Transcriptase Polymerase Chain Reaction,Spinal Cord,Spinal Cord: drug effects,Spinal Cord: metabolism,Spinal Cord: pathology,Superoxides,Superoxides: metabolism,T-Lymphocytes,T-Lymphocytes: drug effects,T-Lymphocytes: immunology},
mendeley-groups = {dextromethorphan},
month = oct,
number = {1},
pages = {63--72},
pmid = {21704706},
title = {{Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and reducing peripheral immune cells infiltration in the spinal cord.}},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3153572\&tool=pmcentrez\&rendertype=abstract},
volume = {44},
year = {2011}
}
</bibtex>