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Re: provigil mechanism of action?

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


> 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:
> And, especially in view of the well-founded concern about glutamergic toxicity:
> Neuroreport. 1998 Dec 21;9(18):4209-13. Related Articles, Links
> Modafinil prevents glutamate cytotoxicity in cultured cortical neurons.
> Antonelli T, Ferraro L, Hillion J, Tomasini MC, Rambert FA, Fuxe K.
> Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
> 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.
> I admit to understanding very little of what I've cited, but Pub Med is a beautiful thing.
> -z




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