![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by emme on January 11, 2005, at 12:09:11
Is there any evidence or thinking about whether provigil can cause neurotoxicity b/c it increases glutamate? Or is the amount by which it increases it too small for that? Does taking it with a benzo cancel it out? Whaddaya think?
Posted by zeugma on January 11, 2005, at 16:23:52
In reply to Provigil - glutamate - benzos, posted by emme on January 11, 2005, at 12:09:11
If I recall correctly (I've read tons of abstracts, and I don't have a printer so I just read them and move on) Provigil does increase glutamate to some degree, but its effect at normal doses (i.e. not the doses they perfuse into exposed rat brain for the purpose of seeing what a month's supply of modafinil would do to naked cytoplasm) is to reduce GABA in certain areas, particularly those connected with motor function. (This is why it's being researched in Parkinson's disease.) It is also a DA reuptake inhibitor, though a relatively weak one, and it exerts strong effects on the hypothalamus, which is one of the brain's key structures: sleep, feeding, coordination of responses necessary to survival are all dependent on a functioning hypothalamus. No one really knows what provigil does, but it does seem to reduce, directly or not, GABA, in certain regions, and thereby indirectly raise glutamergic levels, or at least the ratio between the two, in those regions, which are probably far removed from the amygdala (the benzos' therapeutic site of action.) And I distinctly recall reading an abstract in which provigil protected against glutamate-induced cytotoxicity, though again, one must interpret studies of this kind with caution.. And no, it does not interfere with benzos, at least clonazepam (speaking from my own experience). Its reputation is that of the least anxiogenic of the stimulants.
-z
Posted by zeugma on January 11, 2005, at 16:34:36
In reply to Provigil - glutamate - benzos, posted by emme on January 11, 2005, at 12:09:11
Here is the article on Provigil's supposed neuroprotection against glutamergic cytotoxicity:
Neuroreport. 1998 Dec 21;9(18):4209-13.
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.
Since this was all that came up when I typed the words 'modafinil glutamate cytotoxicity' into the search engine, I assume there have been no more recent studies that contravene this suggestion.Hopefully, minds more trained than mine can look at this and see if it means what it seems to mean.
-z
Posted by emme on January 12, 2005, at 15:00:24
In reply to the wonders of PubMed » emme, posted by zeugma on January 11, 2005, at 16:34:36
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.