So I had a question about tolerances. While I've heard of many drugs leading to all sorts of tolerances (most recreational drugs -> dopamine down-regulation, caffeine -> adenosine up-regulation, nicotine -> acetylcholine desensitation + up-regulation, and some drugs -> enzyme up/down-regulation etc), I realized I've never heard of something causing a norepinephrine tolerance. For stimulants, does this just not occur, or is it just minor in comparison to the dopamine tolerance?
I am wondering this mostly in the context of methiopropamine (MPA), as it is a potent norepinephrine agonst (I believe a re-uptake inhibitor) and a minor dopamine agonist as well. Dopamine effects aside, is it possible to build a tolerance to the pure stimulant effects of drugs that act directly on norepinephrine (unlike caffeine, as it acts through adenosine which will upregulate)?
Thanks
