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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by elise on June 19, 2000, at 19:17:36
I think i really hate this dexedrine stuff. I feel find during the day until about 4, then I feel lousy. I am thinking about possibly trying the provigil again. Is anyone having any success with it? And if so, what dosage? thanks, elise
Posted by Rick on June 20, 2000, at 17:11:19
In reply to Provigil, posted by elise on June 19, 2000, at 19:17:36
> I think i really hate this dexedrine stuff. I feel find during the day until about 4, then I feel lousy. I am thinking about possibly trying the provigil again. Is anyone having any success with it? And if so, what dosage? thanks, elise
Great success as part of my social anxiety cocktail. 200 mg. But I can't say what the results would be if I weren't taking Serzone and Klonopin at the same time. I can say that *small* doses of other stimulating meds (even Wellbutrin) increased anxiety for me when added to Klonopin or a Klonopin/Celexa combo. But not with the Provigil...it actually *increases* my confidence and mental comfort.
Rick
Posted by JohnL on June 20, 2000, at 17:54:24
In reply to Provigil, posted by elise on June 19, 2000, at 19:17:36
> I think i really hate this dexedrine stuff. I feel find during the day until about 4, then I feel lousy. I am thinking about possibly trying the provigil again. Is anyone having any success with it? And if so, what dosage? thanks, elise
We all respond so differently it always fascinates me. After trying Provigil, I have to admit I still favor Adrafinil as the most superior for my particular chemistry. Have you tried it?
JohnL
Posted by elise on June 20, 2000, at 21:15:09
In reply to Re: Provigil, posted by JohnL on June 20, 2000, at 17:54:24
What exactly is adrafinil? Why can you order it without a prescription?
elise
Posted by michael on June 21, 2000, at 13:17:52
In reply to adrafinil, posted by elise on June 20, 2000, at 21:15:09
>
> What exactly is adrafinil? Why can you order it without a prescription?
> elise
\Adrafinil was a med developed in France. The second generation of that med is called modafinil - known in the us by the brand name Provigil.
It, like provigil, is thought to work via stimulation of the alpha-1 receptors - which are the receptors norepinephrine stimulates.
However, they're not exactly sure of the precise mechanism or method of action for either (I believe all of the above is accurate - someon please correct me if I'm mistaken, or add if I've left stuff out)
You can't get it in the states because unlike provigil, adrafinil has not been FDA apporved. In my opinon, most likly because there is no profit incentive. It's relatively cheap, so unlikely to generate $'s to cover lengthy trials, and no $'s for profit thereafter. (Provigil, on the other hand, is very expensive - lots of profit margin)
You can order it from abraod. Some pharmacies may require a prescription, some do not (eg nubrain). You can import up to a three month supply per order, for personal use - FDA rules.
michael
Posted by SLS on June 24, 2000, at 15:36:47
In reply to Re: adrafinil, posted by michael on June 21, 2000, at 13:17:52
> It, like provigil, is thought to work via stimulation of the alpha-1 receptors - which are the receptors norepinephrine stimulates.
>
> However, they're not exactly sure of the precise mechanism or method of action for either (I believe all of the above is accurate - someon please correct me if I'm mistaken, or add if I've left stuff out)
I get the impression that the increased levels of extracellular glutamate produced by Provigil may play a greater role in its effects on mood and wakefulness than does alpha-1 agonism. Most of the newer stuff I see on Medline indicates that alpha-1 receptor pathways must be intact to facilitate the effects of Provigil, but are not necessarily affected directly by it.I'd like to see the original studies that determined the "putative" binding of Provigil to NE alpha-1 receptors. Can anyone provide references? From what I can see, it may not do so at all. The package insert declines to include it as a possible mechanism of action.
I doubt Provigil is an alpha-1 agonist as it does not prevent or mitigate cateplexy in narcolepsy.
- Scott
Posted by JohnL on June 25, 2000, at 5:55:00
In reply to Re: adrafinil, posted by SLS on June 24, 2000, at 15:36:47
>
> > It, like provigil, is thought to work via stimulation of the alpha-1 receptors - which are the receptors norepinephrine stimulates.
> >
> > However, they're not exactly sure of the precise mechanism or method of action for either (I believe all of the above is accurate - someon please correct me if I'm mistaken, or add if I've left stuff out)
>
>
> I get the impression that the increased levels of extracellular glutamate produced by Provigil may play a greater role in its effects on mood and wakefulness than does alpha-1 agonism. Most of the newer stuff I see on Medline indicates that alpha-1 receptor pathways must be intact to facilitate the effects of Provigil, but are not necessarily affected directly by it.
>
> I'd like to see the original studies that determined the "putative" binding of Provigil to NE alpha-1 receptors. Can anyone provide references? From what I can see, it may not do so at all. The package insert declines to include it as a possible mechanism of action.
>
> I doubt Provigil is an alpha-1 agonist as it does not prevent or mitigate cateplexy in narcolepsy.
>
>
> - ScottScott,
You may be onto something here. I used to try amino acid supplements. At one time I focused on glutamate chemistry. I got much worse. I also got worse with Provigil. Coincidence or connection?All I know for sure is that I have tried both Provigil and Adrafinil and they are not at all similar.
Posted by SLS on June 25, 2000, at 8:07:35
In reply to Re: adrafinil, posted by JohnL on June 25, 2000, at 5:55:00
Hi John.
How are you doing these days?
> > I doubt Provigil is an alpha-1 agonist as it does not prevent or mitigate cateplexy in narcolepsy.
> >
> >
> > - Scott
>
> Scott,
> You may be onto something here. I used to try amino acid supplements. At one time I focused on glutamate chemistry. I got much worse. I also got worse with Provigil. Coincidence or connection?
>
> All I know for sure is that I have tried both Provigil and Adrafinil and they are not at all similar.------------------------------------------------------
What sorts of experimentation did you conduct with glutamine/glutamate and what were the results? Is there such a thing as a glutamate supplement?I can't find any detailed information regarding the pharmacology of adrafinil. I have no idea if or how it may affect glutamate/GABA neurotransmission. I am not convinced that modafinil and adrafinil do *not* stimulate NE alpha-1 receptors directly. They may. Different study designs produce different conclusions. However, none of the ones I came across assayed the binding of either of these drugs to NE receptors. All of the evidence for noradrenergic activity was indirect and required deductive reasoning. In the abstracts and articles I have seen, adrafinil and modafinil are described as being "putative" NE alpha-1 agonists, but never refer to specific data demonstrating it. It seems more like hearsay.
Both your differing experiences with modafinil and adrafinil and the notion that NE alpha-1 agonists (naphazoline) can be used as prognosticating probes for their efficacy make understanding the mechanisms of action of these two drugs relevant to treatment. If you encounter anything, please post it.
By the way, did either adrafinil or modafinil affect your appetite or body weight?
*** So... what's your new miracle drug? I want it. Are you taking adrafinil?
Feel well.
Sincerely,
Scott
Posted by JohnL on June 26, 2000, at 4:09:32
In reply to Re: adrafinil, posted by SLS on June 25, 2000, at 8:07:35
Scott,
I'm very well as long as I continue with Adrafinil. Short departures to some other adrenergic approaches did not go well. Adrafinil is my primary medication right now, though I still take 7.5mg Remeron an hour before bed. Removal of either medication causes fairly rapid deterioration, so I'm convinced they both play a role and are working in harmony.
Neither Adrafinil or Modafinil seem to have any effect on weight. If anything, I think someone might be able to lose weight. That's because appetite is slightly reduced and activity is increased. I still get plenty hungry at mealtime, but I don't get the between-meal snack munchies very often.
JohnL
Posted by SLS on June 26, 2000, at 8:14:33
In reply to Re: adrafinil - SLS, posted by JohnL on June 26, 2000, at 4:09:32
The following is an excerpt from a recent Cephalon package insert for Provigil (modafinil). The insert is copyrighted 1999. It details the reasons why it has been concluded that Provigil does NOT bind to and stimulate NE alpha-1 receptors.
"Modafinil does not appear to be a direct or indirect alpha-1 adrenergic agonist. Although modafinil-induced wakefulness can be attenuated by the alpha-1 adrenergic receptor antagonist, prazosin, in assay systems known to be responosive to alpha-adrenergic agonists, modafinil has no activity. Modafinil does not display sympathomimetic activity in the rat vas deferens preparations (agonist-stimulated or electrically stimulated) nor does it increase formation of the adrenergic-mediated second messenger phosphatidyl inositol in in vitro models. Unlike sympathomimetic agents, modafinil does not reduce cataplexy in narcoleptic canines and has minimal effects on cardiovascular and hemodynamic parameters."
I don't know if this information applies to adrafinil. My guess is that it most likely does.
- Scott
Posted by SLS on June 26, 2000, at 8:17:55
In reply to Provigil does NOT stimulate NE alpha-1 receptors, posted by SLS on June 26, 2000, at 8:14:33
Just an observation regarding the few cases I have come across:
People for whom reboxetine has made them feel worse have responded favorably, if only transiently, to either Provigil or adrafinil. People who have responded favorably to reboxetine have not responded to adrafinil.
- Scott
This is the end of the thread.
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