Posted by SLS on June 11, 2000, at 10:27:50
In reply to Re: More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 10, 2000, at 16:42:37
What are the current thoughts regarding the role of NE alpha-1 agonism in the wakefulness-promoting properties of Provigil?
> -- While similar in many ways, different benzos vary in strength and theraputic value. For instance, Klonopin is a high-potency benzo that has been proven very effective in Social Phobia, while Valium usually has no value at all in treating this form of anxiety. Moreover, Klonopin's unique effects in a variety of non-anxiety disorders such as epilepsy, restless leg syndrome, dystonia, and tremor, suggestions a pharmacology which may involve more than simple GABA agonism.
As far as the varied effects of the benzodiazepines are concerned, one factor underlying them may be that there are different subtypes of benzo-receptors to which they bind with varying affinities. In addition, I recall that Klonopin (clonazepam) was thought to have serotonergic properties.
> --If I was reading the studies correctly, the observed GABA-reduction with Provigil (and again, occuring only in selected site/dosage situations) maxed at 20%. (It was hard for me to understand the data as presented. I *believe* the 80% figure cited represented the amount of GABA *maintained* at those sites, but maybe it instead referred to GABA *reduction* levels.) A 20% maximum reduction would proably not have much clinical import, especially if other significant sites were unaffected.
I think 20% may be a pretty big number under certain conditions. Just think what a difference a 20% change in the dosage of a drug can make.
As you have mentioned, an important variable that is sometimes overlooked when attempting to understand the differing effects of drugs and neurotransmitters is in which locations or structures within the brain they accumulate and act.
From what I was able to glean from abstracts, despite my misspelling in the thread below, Provigil increases the extracellular concentration of glutamate in the hippocampus and thalamus. I believe it is this increase in glutamate that is responsible for the inhibition of GABAergic neurons there. Perhaps it is the inhibition of efferent GABAergic pathways that is responsible for the increased release of dopamine in the nucleus accumbens observed with Provigil. This may account for some of its psychostimulant effects - motivation, vigilance, reward-seeking, euphoria. Provigil also has been reported to increase the release of glutamate in the hypothalamus. Through similar mechanisms, this may be what is responsible for its ability to produce anxiety and activation. I don't know what the observed increased release of glutamate in the cerebral cortex is all about.
How would you compare modafinil and adrafinil in the treatment of depression? Is there a trend towards greater "poop-out" with modafinil?
What sorts of effects does adrafinil have on the liver, and what is the rate of occurrence?
- Scott
poster:SLS
thread:36517
URL: http://www.dr-bob.org/babble/20000610/msgs/36923.html