But that's not a directly related to increased noradrenaline levels. Those reuptake inhibitors prevent reuptake in neurones (increasing synaptic levels - outside of that the noradrenaline is rapidly metabolized), but it's not neurones that synthesize adrenaline in the adrenal gland
I would say there is obviously a feedback response. I never claimed that the effect was direct; simply that, directly or not, norepinephrine reuptake inhibition is going to increase blood levels of cortisol and ACTH, which are going to increase circulating adrenaline. These elevations subsequent to NRI are documented in research.
Tsukasa: Again, I apologize for my dumb rudeness. I simply thought this was established, not a matter of dispute.
Methylphenidate is purely a reuptake inhibitor, it doesn't cause dopamine release like amphetamine does
Yeah, my error, I meant to write "striatal dopamine transmission".
Well the path from phenylalanine to noradrenaline goes via dopamine and dopamine exerts a negative feedback effect on tyrosine hydroxylase, so it's going to have negligable effects on noradrenaline levels (which also inhibits tyrosine hydroxylase)
By your formula, how would endogenous, or rather non-supplemented production of norepinephrine by beta-oxidation of dopamine, from l-dopa, from l-tyrosine from l-phenylalanine occur at all?
Supplemental l-tyrosine and l-phenylalanine are known to potentially increase blood pressure, and fight fatigue. These are noradrenergic effects. Pure dopaminergics are typically sedative. If supplementing phenylalanine only caused a significant increase in dopamine, its side effect profile would likewise tend towards sedative effects, hypotension, etc.
D-phenylalanine, if it leads to any significant, relevant increase in PEA, is going to increase norepinephrine transmission that way as well.
Whats all this talk about norepinephrine being a good thing? its the fight or flight chemical, it causes anxiety and stress why would you want to increase that?
It's not 'the' only fight-or-flight chemical. 'All things are with poison ... the dose makes the poison'. It's a neurotransmitter. Without it you'd be dead, and with too little of it you would be in a coma, etc. Too much, as you mentioned, is associated with fear, anxiety, stress, and at extreme levels perhaps stroke, etc.
It can facilitate concentration and reduced hyperactivity by leading to a stimulation of prefrontal structures -- this is the effect presumably sought with atomoxetine.
With norepinephrine reuptake inhibitors as antidepressants, the benefits IMO are likely to be downstream, a consequence of regulatory responses.
I certainly think that there are situations or bounds within you would not want increased norepinephrine transmission, as dependent on individual variations and considerations. For instance, in my individual case, for various reasons I mentioned elsewhere* I have been lead to an interest in inhibiting overall norepinephrine transmission from my medicine regimen, perhaps by adding theanine or guanfacine as adjunct to my d-amp.
*(classic (nor)adrenergic side effects like appetite suppression, and because of what I believe is a possible decrement in cognitive flexibility, and functionally, creativity)
