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How potent is Mirtazapine considered to be on NorAdrenaline - vs other tetra/triC.

The study indicates a low increase of DOPAC increase with Mirtazapine in the striatum, which is saying lower NE related effects with Mirtazapine for striatum, but similar NE levels elsewhere apparently. It could be that Mianserin doesn't effect NE in the striatum either but seeing as they didn't mention that, they were probably implying that that was an abnormality specific to mirtazapine.

The lack of serotonergic effects with mianserin could possibly be due to NRI and/or differential affinity for a2a vs. a2c presynaptic receptors with differential expression of a2a and a2c across cell types.

For example, what if Mianserin had higher affinity for a2a which was more predominantly expressed on NE neurons compared to mirtazapine which might have lower (relative to Mianserin) affinity for a2a and higher affinity for a2c which could be expressed more so on serotonergic neurons? Just conjecture though.

And I can't recall where I remembered that study from, was probably searching for more about the a2 autoreceptors.
 
I t hought norepinephrine was mostly in the prefrontal cortex with dopamine transporters playimg a largerr role in the straitium because it controls more basic drives and emotion Vs Attention cognition.
 
Did you mean to type "I thought norepinephrine transporters were mostly in the PFC with dopamine transporters playing a larger role in the striatum"?

It is true that there's a very low level expression of DAT in the PFC, but dopamine itself still plays important roles there and of course NE does as well.
 
Sorry, typing skills are horrible on my phone because the screens cracked. xD But, yes I mean if the goal is focus and attention type effects wouldnt a lack of noradrenaline increase in the stratium not necessarily mean it doesnt effect noradrenaline in parts of the brain more involved in cognition. I hope that makes sense It sounds confusing now that I read it.
 
No worries, and oh okay I see what you're saying now.

Yes that's certainly true, I'm sure it impacts NE release in more NE relevant areas. But there are more midbrain areas like the Ventral Tegmental Area that are important for executive function etc that are primarily dopaminergic/GABAergic (just pointing out that not all cognition is due to solely the cortex functioning properly)
 
True speaking of which i just had wayyy too much noradrenaline and its really not just noradrenaline i actually felt less focused be abuse my ears where ringing and i felt shaky. Nicotine helps my focus must as much id say. Esp the combo because without it i just feel like wired. Noradrenaline type drugs seem to get me ready to go and going but nicotine helps me stay not to fast and really focus on details.
 
Nicotine seems to be used by schizophrenics especially to help with cognition, it certainly dose help some people.
 
d1nach said:
True speaking of which i just had wayyy too much noradrenaline and its really not just noradrenaline i actually felt less focused be abuse my ears where ringing and i felt shaky. Nicotine helps my focus must as much id say. Esp the combo because without it i just feel like wired. Noradrenaline type drugs seem to get me ready to go and going but nicotine helps me stay not to fast and really focus on details.
Click to expand...

What
combination are you taking that is focusing so acutely on noradrenaline??
 
Effexor(150Mg), amphetamine(55mg), caffeine (12-20 cups), and modafinil (400 mg), nicotine > 40 mg per day.
 
That doesn't seem too much noradrenaline specifically.

Did you not mention you had atomoxetine/straterra in there somewhere?
 
Saw my doc yesterday.

He's recommended Lofepramine.

He's left it up to myself whether I want to replace the remeron or wellbutrin, with the lofepramine.

I'm thinking, cut the remeron down to 15 mg and continue to use as a sleep aid.
Then introduce the lofepramine.

I think I could possibly get my hands on mianserin also, but he's recommended this so.....?

It's like, a noradrenergic tricyclic.
 
Hmm - the clinical data and binding values on wikipedia seem to distinctly contradict that which is in various pieces of literature, regarding lofepramine.

But also - desipramine.

It's ki values on wiki are 17 nM for SERT.
Other pieces of literature suggest far weaker at 180 nM.

Wiki also suggests lofepramine metabolite, desipramine, does not play an active role in its anti-depressant efficacy.

https://www.ncbi.nlm.nih.gov/pubmed/10379421/

This pubmed article flat out contradicts that.

What exactly is going on here?
 
Im not trying to jack up noradrenaline it just so happens they boost dopamine and noradrenaline. I stopped strattera because it was a compromise with my doctor and it was pretty weak compared to adderall imo esp for mood
 
It's really not uncommon for people to report all sorts of different findings.

But I bet the metabolites are playing the larger role in its effects though, I'm assuming there are more metabolites at play
 
Desipramine (10) has Ki values of 7.36,163 and > 10,000 nM at rat NET, cloned human SERT and rat DAT, respectively (31). Both nortriptyline (11) and protriptyline (12) have a similar tricyclic structure as desipramine. Nortriptyline is a more potent inhibitor of the NET (Ki = 3.4 nM) than the SERT (Ki = 161 nM)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518795/


These values are flat out hella different to the logged wikipedia values.
Claiming nortriptylines effect on SERT is 17.5 nM - hmm?

If Desipramines true SERT binding value is in the 180 nM range - it has a super low anti-cholinergic value, low antihistamine, very tight NET binding.
Then it would basically be my dream drug; well, dream to try next at least.
 
I've been sifting through academic paper after academic paper attempting to find the IC50 values for the different noradrenergic agents.

I think I have desipramines.... but need to find those for maprotaline, mianserin, lofepramine, nortriptyline, atomoxetine and reboxetine - for comparison.

Instead of making a new thread.....

Opinions:

A combination of what I currently take: Mirtazapine, Bupropion - full doses of both - with, lofepramine?

I understand lofepramine is not a potent anti-histamine - so no worries about exacerbating that with mirtazapine.

Looking at the receptor subtype activity, there's certainly no potential for serotonin syndrome.
Risk of seizures?

Generally a possible combination?

I have a friend who's on effexor and lyrica combo - but 30 mg mirtazapine at night, for sleep.
Triple combo.

Alternative might be to do a dual combo with bupropion + atomoxetine daytime, mirtazapine at night.

Opinions?

Intensify the noradrenergic effect as much as possible.
 
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