Posted by SLS on March 2, 2006, at 20:57:02
In reply to Re: provigil mechanism of action?, posted by zeugma on March 2, 2006, at 20:21:17
That's a lot of stuff to consider.
I think excitotoxicity is the result of excessive calcium influx, and not the presence of glutamate per se. Gosh, I would have to do a bunch more research to even pretend that I understand any of this. It might depend on the location(s) of the increased extracellular glutamate as to whether modafinil is neuroprotective or neurotoxic.
'Tis a puzzlement.
- Scott
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> i am just going to post to make this discussion even more confounding than it's been (I mean discussing modafinil's mode of action, not the discussion itself). Modafinil is classed as a 'neuroprotective agent,' and there have been numerous studies on a so-called 'neuroprotective' effect:
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> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15000882&query_hl=3&itool=pubmed_docsum
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> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10580713&query_hl=5&itool=pubmed_docsum
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> And, especially in view of the well-founded concern about glutamergic toxicity:
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> Neuroreport. 1998 Dec 21;9(18):4209-13. Related Articles, Links
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>
> Modafinil prevents glutamate cytotoxicity in cultured cortical neurons.
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> Antonelli T, Ferraro L, Hillion J, Tomasini MC, Rambert FA, Fuxe K.
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> Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
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> The ability of modafinil (Modiodal) to protect cortical neurons from glutamate-induced degeneration was evaluated by measuring electrically evoked [3H]GABA release and [3H]GABA uptake in primary cerebral cortical cultures. In normal cells, electrical stimulation (10 Hz, 2 min) increased [3H]GABA release (FR-NER St1 = 0.77+/-0.14; St2/St1 ratio = 0.94+/-0.02). The exposure of sister cells to glutamate, reduced electrically evoked [3H]GABA release (FR-NER St1 = 0.40+/-0.05; St2/St1 ratio = 0.60+/-0.08). Modafinil (0.3-1 microM) prevented the glutamate-induced reduction of the St2/St1 ratio (0.85+/-0.11; 0.88+/-0.05, respectively). A similar protective effect was observed for [3H]GABA uptake. These findings suggest that modafinil may be neuroprotective in that it attenuates glutamate-induced excitotoxicity in cortical neurons.
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> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9926875&query_hl=9&itool=pubmed_docsum
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> I admit to understanding very little of what I've cited, but Pub Med is a beautiful thing.
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> -z
poster:SLS
thread:612884
URL: http://www.dr-bob.org/babble/20060227/msgs/615159.html