Posted by zeugma on August 22, 2004, at 13:39:04
In reply to Re: are stimulants neurotoxic? thanks in advance., posted by alesta on August 22, 2004, at 11:20:34
> hi, ame!
>
> thank you! good to see you again!
>
> considering the cardio strain involved, wouldn't it be better for people to take provigil instead, as it is different from the other stimulants in that it doesn't produce the typical negative side effects of stimulants? and strattera for adhd, since it isn't a stimulant at all? thanks....
>
> amy:)
>
>
hi amy, i want to note that I was on Strattera for a year, and yes, it was very helpful for a time. But the drug is more complex than advertised, as in fact most drugs tend to be. I experienced an anhedonic, anergic depression, which is unusual for me in that while I am normally pretty anergic (my caffeine intake is MASSIVE and that's just to stay awake) anhedonia is not something I've experienced often, although I am certainly not someone who has accumalted a massive amount of 'hedons' as J.S Mill would call them, as would be expected of someone who's suffered from nearly lifelong depression.Anyway, I believe the cause for Strattera's nasty side effects has been discovered:
Bioorg Med Chem Lett. 2004 Aug 2;14(15):4083-5. Related Articles, Links
Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect.Creighton CJ, Ramabadran K, Ciccone PE, Liu J, Orsini MJ, Reitz AB.
Drug Discovery, Johnson and Johnson Pharmaceutical, Research and Development, Spring House, PA 19477-0776, USA. ccreight@prdus.jnj.com
The major human metabolite of atomoxetine (4-hydroxyatomoxetine) was tested against a panel of receptors and enzymes, and was found to interact with the mu, delta, and kappa-opioid receptors based upon studies involving both binding and functional assays. 4-hydroxyatomoxetine was determined to be a partial agonist of the kappa-opioid receptor.
The opioid activity of this metabolite, which the manufacturer claims circulates at only 1 percent of the concentration of the parent drug, is probably responsible for the numerous reports of fatigue, unwanted sedation, and just plain depression that have surfaced about this drug. It is substantially less protein bound than the parent, and it is estimated to circulate in plasma at approximately equal concentrations to atomoxetine itself, in normal metabolizers of the drug.
I have read the leading psychopharmacologists of the world (Dr. Stahl and company) debate this sedating effect, in the absence of this newly surfaced data, and they specualte that it must be a 'paradoxical' effect surfacing from stimulation of alpha-1 or alpha-2 receptors. This explanation was one I immediately distrusted, because reboxetine which is quite similar to atomoxetine tends to produce complaints about overstimulation, not fatigue, and desipramine which is also quite similar to atomoxetine generally is also on the stimulating end of the spectrum (though not of course a stimulant).
Provigil is a reasonably effective drug (for me at least) but its benefits were counteracted by its half-life, which is longer than that of the other stims, and which caused a major insomnia problem for me. I wish I could have taken it, because I am at risk for cardio complications due to the TCA I take, and I require a stimulant of some kind besides just caffeine. So I'm on a tiny dose of Ritalin LA, and trying to make the best of it.
-z
poster:zeugma
thread:380741
URL: http://www.dr-bob.org/babble/20040821/msgs/380862.html