Drugs implicating Catecholamine activity and effect - directly or indirectly?

[JohnBoy2000]

Basically - question being, what are these drugs?

Amphetamines and cathinone like drugs, stimulants, increase noradrenaline, subsequent activity, cognizance, energy - and also heart rate and sympathetic effects.

What's come to my attention more recently is, just as being hyperthyroid increase catecholamine sensitivity resulting in, by example - accelerated heart rate etc, hypothyroidism or thyroid deficiency, does the opposite; decreases catecholamine sensitivity, resulting in lethargy etc.

Question is simply - what else implicates catecholamines and these effects?

That which would most notably give rise to the fatigue/lethargy effect?

The primary consideration in general medicine does indeed seem to be the Thyroid.

But just for a more comprehensive understanding of the area - what other considerations would one take into account when approaching catecholamine activity?
i.e. Stimulant drugs, thyroid activity...... what else?

And just for clarity - it would be catecholamine activity more specific to the brain/neurons, versus other physiological systems, so would be precluding "adrenaline"; noradrenaline being more so the focus.

 

[AlphaMethylPhenyl]

This doesn't sound advanced.

The fight or flight response.

But I still don't understand your question. Maybe look up the HPA and how it functions. The hypothalamus tells the pituitary gland to tell the adrenal gland to release hormones, such as nor/epin. But not all nt's are hormones. Hormones are released into the bloodstream.

A lot of people take thyroxine to counter hypothyroidism, which could be to counter aging effects, and oftentimes it's given to people on lithium. Lithium can do a number on a few organs and their function. But it's still the gold standard for bipolar disorder and has a plethora of mechanisms as one unqiue package. The therapeutic ratio is low, so people have to get blood tests while on it. This stands as a testament to its value in the industry.

Novelty will get you going. Pick up a new habit, read a good book, and so on. The best way is the most natural one. Perhaps adaptogens can help. They're medicinal, but there isn't a lot of literature on them because there's not a lot of profit to reap.

So if you more about the material you'd know that nor/epin. are so closely structurally related to dopamine and that that the former metabolize into the latter, that you can't have the central effects without peripheral stimulation. Same with other catecholamines. I.e there is no such thing as an SDRI. Significantly serotonergic stimulants tend to be cardiotoxic and/or neurotoxic--I realize this is contentious, but it's my substantiated belief. But this is easier to understand: stimulants bring you up. And what goes up must come down. That comedown isn't just the drug leaving your CNS, it's also about metabolic reactions (dopamine to nor/epin. and so on).

Make sense? Anything else? Did I answer your question?

 

[JohnBoy2000]

I understand what you're saying in terms of the up/down effect.

But who knows if there's some intrinsic dysfunction in noradrenaline process in my case.

So - NRI's worked like rocket fuel for me before, but with intolerable effects on personality so, unsustainable.

I take a high dose Levothyroxine/T4 and it seems to boost noradrenaline effects also (via "permissiveness" - the thyroid/NA synergy).


Having looked a little more - apparently methylation can implicate production of catecholamines also.
Some kind of mutation in some genes called MTHFR and COMT; methylation doesn't go down correctly so noradrenaline may not be produced sufficiently.

My question was, as to being comprehensive - what we've got so far,

- Thyroid function via synergy implicates catecholamine function

- Methylation dysfunction can hamper catecholamine process

What else is up for consideration?
Any other molecular/biochemical/genetic process or function that hamper or implicate catecholamine/noradrenergic function and effect?

i.e. Thyroid hormone replacement therapy and using methylfolate can act as "uppers" for those with genetic noradrenergic dysfunction.
What else can do this?

 

[AlphaMethylPhenyl]

I mean, other than COMT, MAO-A and more so MAO-B inhibitors increase catecholamines in terms of net binding. But I don't know if that's what you're looking for.


There are tons of reasons or connective factors why one could have more or less of an ideal amount of them. Parkinson's disease, ADHD, dementias in general, heavy stimulant abuse, certain kinds of depression for less. Anxiety disorders/opioid withdrawal more.

 

[JohnBoy2000]

COMT - that can be looked into via gene mutations, the likes of 23andme etc?

MAO enzymes - if there were gene mutations here, they'd ultimately be treated via psychiatric drugs like MAO inhibitors and/or transporter blockers etc like atomoxetine etc?

Anything other considerations when looking at MAO?

COMT mutation basically disrupting the methylation cycle, so apparently there's alternate treatments that implicate this like taking active/methyl cobalamin/folate and SAMe?


Basically anything - ANYTHING - that enhances noradrenergic function, outside of traditional NRI's, be they prescription or recreational amphetamine etc??

Thyroid increasing catechol/NA sensitivity was a revelation to me;
Just curious as to whether there's other revelations I may have missed?

 

[d1nach]

Honestly in my experience drugs like nris and amphetamines ect are infinitely stronger then when i took folate and same. Maybe if you had a folate deficiency but idk man im not convinced on the folate and same if it is so effective why do we use comt inhibitors for l dopa. I dont think the evidence while it looks conviencing for folate or same are anywhere near pharmacuticals hence imo prob why i could just go buy them. If they where point wed have people going into hypertensive shock or some crazy stuff.

 

[AlphaMethylPhenyl]

Most of this is theoretical. They have found people with higher MAO to be depressed.

Why are you so bent on this? Lots of people think they know their biochemistry based on very basic psychpharm.

Honestly what are you hoping to achieve here?

 

[JohnBoy2000]

Most of this is theoretical. They have found people with higher MAO to be depressed.

Why are you so bent on this? Lots of people think they know their biochemistry based on very basic psychpharm.

Honestly what are you hoping to achieve here?

Looking for answers.

I refuse to believe I went from being an energetic, nothing can stop me type of individual - to chronically dysfunctional, perpetually lethargic mess - for no reason.

Anything that seems to implicate BMR, presumably by affecting noradrenergic response - when that's optimized - feels like I'm perfectly well.

MTHFR and COMT are precursors to NA production so, it makes sense to explore that further.

Thyroid synergizes with NA function, and it's yielded somewhat of a result.

Throw all that in the mix with the fact that directly acting psychoactives such as NRI's, mirtazapine etc - have an unquestionable, but seemingly medically uncharacterized effect on personality, and suddenly there's this conundrum which general medicine seems to have no real direct answer to.


So, as above - I'm just looking for anything else that may or may not be even theoretically implicated in noradrenergic function?
Downstream, synergistically, via permission - etc?

That's my overarching question here.

And I'm asking simply because, it would seem clear that whatever the precipitating factor of my symptoms, it's related to NA function - from some direction, somehow.

Now enhancement via traditional NA enhancers like NRI's - rocket fuel - but unsustainable.
Cause it would seem, whatever has given rise to the base dysfunction, may be temporarily masked by the likes of NRI's, but they don't solve the underlying problem.

Honestly in my experience drugs like nris and amphetamines ect are infinitely stronger then when i took folate and same. Maybe if you had a folate deficiency but idk man im not convinced on the folate and same if it is so effective why do we use comt inhibitors for l dopa. I dont think the evidence while it looks conviencing for folate or same are anywhere near pharmacuticals hence imo prob why i could just go buy them. If they where point wed have people going into hypertensive shock or some crazy stuff.

I'd tend to agree via the greater potency of directly acting NRI's.

However, the effect of these with myself, feels oftentimes, too direct.
I guage this via, frankly the variation in personality they seem to give rise to, and thus the less favourable interpersonal responses they seem to also give rise to ("get out of my face, dammit!").
Real direct.

So, something that perhaps implicates noradrenaline but, less directly?
Looking at it's production via MTHFR/COMT - ess posible?

Then the thyroid via permissiveness or NA effect - also possible?

And then..... what else could be up for consideration?

 

[d1nach]

Gave you tried the alpha and beta adrenic receptors? Esp the alpha in the brain and maybe beta in the peripheral for blocking some of the side effects .

 

[JohnBoy2000]

Gave you tried the alpha and beta adrenic receptors? Esp the alpha in the brain and maybe beta in the peripheral for blocking some of the side effects .

Hell yes.

I've bombarded alpha neural receptors with every psychoactive known to man.
Mirtazapine, mianserin, reboxetine, SNRI's, atomoxetine, methylphenidate etc.

They worked - rocket fuel - but it's the negative implications on personality and other peoples responses to me on these, that really don't make them feasible.
Makes me think, they're acting as a booster add on, when the intrinsic engine itself is malfunctioning in some other capacity.

Beta blockers..... no symptom improvement, tried 'em.


Thus - other factors indirectly effecting adrenergic/noradrenergic process - i.e. COMT, thyroid etc?