[paula_w]

http://michaeljfox.org/newsEvents_pa...cle.cfm?ID=263


paula

[rosebud]

I rarely have dyskinesia problems which is amazing considering I've had this for 10 years and take a truck load of drugs every day of my life. However I shall no longer leave home without my Robo... because when I do have dyskinesia problems they are almost worse than off times. I'll let you know next time I run into the problem how the cough suppressant works.....

I love the line where they say BMY-14802 was "safe but not effective" in treating schizophrenia!!!! I'm sure a lot of schizophrenics were releavieved to hear it was safe....still laughing at that one!

take care and thanks for the invaluable info ....cheers, Joy

[ashleyk]

The NIH has done a lot of research with Dextromethorphan and similar substances that show that DM, in very low doses, can attenuate neuroinflammation and be neuroprotective in rodents which were induced to have Parkinson's. There was a long thread here on DM with some people taking 5mg (1/2 tsp) of DM cough syrup at night, hopefully, to stop PD progression.
Ashley



http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus


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) -induced 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 findings suggest a novel therapeutic concept of using "ultra-low" drug concentrations for the intervention of inflammation-related neurodegenerative diseases.


http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t_uids=9613730

[RLSmi]

I find this very interesting. However, I want to distinguish between both the reason and manner in which I use dextromethorphan (DM) and how it is apparently being tested here for controling dyskinesia.

I am using it as a neuroprotectant by taking a very small dose, 4-6 mg, once each day, just before bedtime. This is based on my extrapolation of the low-dose-naltrexone model of postulated neuroprotection to DM due to the fact that both naltrexone and DM are so-called morphinans, and that they have both been shown by J-S Hong's pharmacology research group to supress the inflammatory response of mouse midbrain microglial cells to bacterial lipopolysaccharide. These drugs decrease the secretion of superoxide and other endogenous "inflammogens" which damage the dopamine neurons in these culture preparations so that they are either killed or rendered less able to either take up or synthesize dopamine. AshleyK and I have both provided references for this work in previous posts.

The intermittent, very dow doses of the drugs (or at least of naltrexone) seem to be important for their neuroprotective function, according to Zygon's work on stimulation of met-enkaphalin formation and production of its cell receptors. It seems to be the action of this endorphin on microglial cell receptors that diminishes their inflammatory behavior. See the LDN.org web page for this explanation.

I am using DM instead of naltrexone simply because it is available over the counter (so far). (See my recent "paranoid" thread.)

As implied by the word "neuroprotection", this strategy, if it works, should at least slow the deterioration of remaining neurons, rather than restore those that are past saving. Probably the best that can expected is arrest of progression of motor symptoms. I have no idea if there might be potential for arresting progression of non-motor symptoms using the low-dose approach.

The effect of diminishing dyskinesias may be something entirely different. I assume that much higher doses of DM or the other drug under study are used to achieve.

Thank you, MJF!

[stevem53]

Nyuk..Nyuc..Nyuk..Nyuk..Nyuk