The D1 up-regulation is after chronic use and it doesn't explain the acute effects of sulbutiamine. The acute effects seemed to be lower DA and unchanged DA receptors... but with a decrease of kainate binding sites. Never even heard of kainate before. How would those acute changes account for the energy and motivation I've been hearing about? Seems paradoxical. Animal's oscillation hypothesis is by far the best one yet. It's also the only one I've heard, can't really say I understand it fully yet though.
A guess about the long-term effects would be that the acute lowering of DA would result in D1 up-regulation over time and that tolerance builds to the motivational aspects.
A wild and speculative hypothesis: When I've built a steady tolerance to the acute effects of sulbutiamine I might still benefit from chronic use by taking it nightly to up-regulate D1 receptors? Anyone thought of this or perhaps even tried it already?
My guess is that, since there are only 22 studies on sulbutiamine in medline, its mechanisms aren't fully elucidated, and trying to draw conclusions based on that one study concerned with DA might not be possible. Involvement of the cholinergic system [1
] raises another possibility for acute mechanism, but the nature of the reports I've read make it sound pretty likely that DA is involved. So perhaps while acute administration decreases prefrontal DA, it is increased in subcortical areas (don't have the text yet, so I have no clue how many variables the study considered).
Looking forward to hearing more about your experience, as I've been curious about this one for a while. Many people seem to take a higher dose for acute stimulating/motivating effects, something like 600-1000mg, IIRC. People who mention the word "workout" seem to be happy with sub-500mg dosages. Chronic dosing would certainly be a worthwhile experiment, but I agree with Animal that many reports suggest that long-term usage sounds like it has some unpleasant drawbacks, at least in some cases. Though a few studies [2
] administered 600mg for 1-2 months, and mentioned no downsides in the abstracts.
In rats sul = no change in # of NMDA
In rats sul = decrease in kainate
In rats sul = no change in D1 density
In rats sul = decrease DA and decrease DOPAC
Is the reason for the decrease in DA and DOPAC because of hydrogen peroxide caused by sul?
The study did mention that chronic treatment increased D1 sites, while acute administration had no effect. Unless the full texts mention something, I didn't see anything to suggest that sulbutiamine increases H2O2 levels. In the absence of such data, it's probably more reasonable to assume that it effects modulation of DA through interaction with receptors or synthesis/release mechanisms, rather than destructive radical damage (which would probably have to be pretty heavy to change levels significantly, and would probably present other symptoms), though it's certainly not out of the question.