Pharmacological interaction between Bupropion and Ritalin?

[JohnBoy2000]

I had read that one potentiates the other.

Well - I tried 10 mg ritalin, about 3 hours after taking 150 mg bupropion.

I simply cannot concentrate, and am having trouble sitting still.
I was studying just find up until 40 minutes ago, and the the ritalin seemed to start working, and I was experiencing feelings of inexplicable happiness - and then I noticed I had to read the same sentence 4 or 5 times, to find meaning in it.

So just now I gave up studying for today, and I suppose I'll have to wait another 2 to 4 hours for the ritalin to wear off.

The feelings of happiness are certainly not unwelcome, but it's like I'm too hyper to concentrate properly.

I'm curious as to wait exactly would give rise to this effect?

Dopamine potentiation?
Because I was previously under the impression that dopamine was sedating - and from what I'm been reading on anti-psychotic mechanisms - D2 antagonism does give rise to sedation.

That being said, D2 agonism in pramipexole - I also found very fatigue inducing/sedating.

Ritalin acting as an NDRI - I'm curious as to claims that increases NA and DA neurotransmission - I was under the impression that transmission would downregulate as a product of an excess of the two chemicals in the synaptic cleft.


I'll leave the OP at that for fear of rambling, as I am very aware that I'm lacking a sufficient level of awareness just now.

PS - is this feeling typically what would be known as "mania" - that which bipolar patients experience?

 

[Cotcha Yankinov]

The yerkes-Dodson law describes the relationship between arousal and performance. There is a non-monotonic response to dopamine and NE in the PFC - that is to say that more is not always better. The way this was explained to me was with working memory. Normally D1 activation in the PFC will help you remember a stimulus after it disappears by increasing the signal to noise ratio. To keep the correct cell ensembles (that represent the stimulus) firing, there is a careful balance between excitation and inhibition. Normally D1 facilitates that by silencing neighboring noisy cells if you will, but too much D1 activation can also silence the cells the represent the stimulus.

So more is not always better. Some ADHD/ADD genes have been linked to a decreased number of dopamine receptors. These people can probably take more stimulants without being pushed into that range where dopamine and NE start to affect performance negatively.

The receptors will eventually downregulate with increased synaptic concentrations of dopamine etc. but that can take a while.

Mania is kinda hard to describe. It's kind of like watching 10 TVs tuned to different channels at once in my experience, YMMV.

 

[Nagelfar]

I've noticed that activating monoamine re-uptake inhibitors ('major depression' diagnosis aimed serotonin, NE & DA effecting drugs) : e.g. Zoloft/setraline, Prozac/fluoxetine, Effexor/venlafaxine & Wellbutrin/bupropion (as opposed to Celexa-Lexapro/citalopram-esCitalopram, Paxil/paroxetine etc., the bi-polar drugs meant not to induce mania in the routine use of them) sedate and make one sleepy, if not titrated up from a non-immediately efficacious dose over time: thereafter such are, for the most part, quite "stimulating". This not-so-anomalous paradoxical reaction is almost like the prospect of 'over-amping' from (meth)amphetamine, where using so large a dose at once can immediately 'put one out' or make you fall asleep until your neurological baseline condition reaches an equilibrium for functionality (by which time you wake back up; just moderately, more or less, stimulated.)

 

[JohnBoy2000]

That filtered out, thankfully.

Quite unpleasant.
Won't be doing that again.

But - it did get me thinking about a quote from Pubmed, where Stephen Stahl suggested a combination of Bupropion, with another noradrenergic - Reboxetine, to potentiate the noradrenergic effect.
That quote was supposedly taken out of "Essential pharmacology" - but upon reading it, I came across the "heroic combinations" - actually bupropion with a stimulant was mentioned in there, oddly.
Though I am also taking mirtazapine, which may have led to further unpleasant potentiation.

But I couldn't locate in the book itself, where the bupropion + reboxetine combination was mentioned.

Is anyone familiar with such?

I'm curious about the drug interactions with reboxetine - there doesn't seem to be a whole lot of information on it, and Stahls prescribers guide only mentions to avoid taking it with MAOI's.

Apparently it inhibits CYP2D6 - I don't know how that is implicated in bupropion or mirtazipines metabolism....?
Bupropion also inhibits this enzyme - but isn't that involved in its actual metabolism - how does that work?
It inhibits the enzyme that metabolizes it?

Anyways - feasible combination - reboxetine + bupropion?