Posted by SLS on February 28, 2006, at 7:11:41
In reply to Re: provigil discussion » Larry Hoover, posted by zeugma on February 27, 2006, at 16:57:26
I don't think adrafinil is a NE alpha-1 receptor agonist either.
I lost a great deal of information regarding adrafinil and modafinil when my last hard disk crashed. Some of it displayed the molecular differences between the two drugs; a difference that involves the cleaving of a single oxygen atom. I'm not sure if adrafinil is simply acting as a pro-drug in the body where it is quickly metabolized to modafinil or if it carries with it properties that are different from modafinil. A single atom can make a huge difference! In any event, adrafinil was invented in the late 1970s when only a handful of amine receptors had been discovered and assayed. I think most of the talk about adrafinil being a NE alpha-1 agonist relied on a single study using faulty logic. It seems that for adrafinil (and modafinil) to exert its stimulant effect, at least one NE alpha-1 receptor pathway needs to remain intact. They found that to administer a NE alpha-1 antagonist (prazosin?) reversed the stimulant effect of adrafinil. They then proceeded to conclude that adrafinil must therefore be a NE alpha-1 receptor agonist. Of course, this deduction completely ignores the possibility of actions upstream of the NE alpha-1 tracts. The study design was fine. It was the conclusion by the authors that was faulty. Almost every subsequent study cited the faulty one as a platform for their own. The error was perpetuated for many years.
- Scott
poster:SLS
thread:612884
URL: http://www.dr-bob.org/babble/20060227/msgs/614182.html