Dopamine And Dopamine Agonists Inhibit Serotonin Synthesis

[haidut]

It is well known that higher dopamine and the use of dopamine "agonist" drugs like bromocriptine, pramipexole, lisuride, etc leads to increased libido. This is explained mostly through the actions of dopamine on the CNS. However, this study claims (in agreement with Peat) that dopamine and dopaminergic drugs also have a direct inhibitory activity on serotonin synthesis by inhibiting the enzyme tryptophan hydroxylase (TPH). The pro-libido drug pCPA also inhibits TPH and lower serotonin leads to dramatic increases in testosterone synthesis. This would explain the studies showing reversal of hypogonadism in males by drugs like cabergoline, bromocriptine and lisuride. In addition, lower serotonin leads to increased metabolism and has been proposed as viable cure of obesity. I posted some studies showing cabergoline and lisuride essentially reversing obesity, even in people with diabetes (II). And all the weight loss was fat mass while preserving muscle mass.
So, for people struggling with high serotonin or any of its associated conditions, it seems that dopaminergic drugs may lower serotonin directly in addition to lowering prolactin.

http://www.sciencedirect.com/science/ar ... 0580904737

"...PCPA, dopamine and the dopamine agonist epinine inhibited trytophan hydroxylase activity in nervous tissue homogenates of and (Bivalvia). Haloperidol did not affect tryptophan hydroxylase activity in the homogenates nor did it antagonize dopamine action."

The drug epinine used above is a metabolite of this drug, and is a D1 agonist:
Ibopamine - Wikipedia, the free encyclopedia

And here is another study, probably more relevant to humans. Interestingly, vitamin C and reduced glutathione prevented the TPH inhibition by dopamine. DMSO did not, and if anything was mildly synergistic to dopamine.
Dopamine inactivates tryptophan hydroxylase and forms a redox-cycling quinoprotein: possible endogenous toxin to serotonin neurons. - PubMed - NCBI

 

[Parsifal]

So people with high prolactin have low dopamine and lack of motivation, ADHD?

 

[haidut]

post 106234 So people with high prolactin have low dopamine and lack of motivation, ADHD?

Yes, semi-dopaminergic drugs even as toxic as the amphetamines AdderAll and Ritalin help ADHD.

 

[Coldhandsandfeet]

Of cabergoline, bromocriptine and lisuride which is the least likely to cause constipation?

 

[haidut]

post 106248 Of cabergoline, bromocriptine and lisuride which is the least likely to cause constipation?

None of them are really known to cause constipation in typical doses. Antagonists of 5-HT3 like ondansetron and mianserin / mirtazapine and even cyproheptadine are much more likely to cause constipation even in low doses.

 

[Coldhandsandfeet]

post 106256

post 106248 Of cabergoline, bromocriptine and lisuride which is the least likely to cause constipation?

None of them are really known to cause constipation in typical doses. Antagonists of 5-HT3 like ondansetron and mianserin / mirtazapine and even cyproheptadine are much more likely to cause constipation even in low doses.

Okay. I find lisuirde to be pretty constipating in small doses.

 

[michael94]

the posts are appreciated keep em coming...

 

[Blossom]

post 106270

post 106256

post 106248 Of cabergoline, bromocriptine and lisuride which is the least likely to cause constipation?

None of them are really known to cause constipation in typical doses. Antagonists of 5-HT3 like ondansetron and mianserin / mirtazapine and even cyproheptadine are much more likely to cause constipation even in low doses.

Okay. I find lisuirde to be pretty constipating in small doses.

Lisuride used to cause me constipation in small doses too. I just started it again after taking a break from it and find it less constipating this time around. Maybe it's just my metabolism improving?

 

[franko]

post 81885 So, for people struggling with high serotonin or any of its associated conditions, it seems that dopaminergic drugs may lower serotonin directly in addition to increasing dopamine and lowering prolactin.

Do you think there is any danger in dopaminergic drugs inducing what would effectively be "dopamine resistance" ?

High bursts of dopamine seem to produce that effect, as seen in drug addicts, but if drugs are used to raise dopamine to normal / physiological levels I wonder if there will be any negative effect...

 

[michael94]

post 106327

post 81885 So, for people struggling with high serotonin or any of its associated conditions, it seems that dopaminergic drugs may lower serotonin directly in addition to increasing dopamine and lowering prolactin.

Do you think there is any danger in dopaminergic drugs inducing what would effectively be "dopamine resistance" ?

High bursts of dopamine seem to produce that effect, as seen in drug addicts, but if drugs are used to raise dopamine to normal / physiological levels I wonder if there will be any negative effect...

As an anecdote, I don't know of any person who exercises intensely on a regular basis and is depressed. Of course if they weren't eating enough that would lead to problems and there's always outliers.

http://www.ncbi.nlm.nih.gov/pubmed/3110847

Then there's obviously diet which likely plays a big role in dopamine receptor density/sensitivity but I haven't done much digging into that specifically. It clearly affects transport and overall levels. I suspect there's other things like meditation which might help but anaerobic exercise still remains the most fool proof way to go about fixing depression in a sustainable way.

EDIT I want to add that to the meditation thing that motivation/happiness for humans is more complicated than just diet/exercise, at least with regard to set-points ( the body loves homeostasis after all). A career you find fulfilling for example goes a long way and that's just scratching the surface. EDIT

The easy route of just taking some dopaminergic drugs should be taken with caution, especially as a long term solution.
Short term and with smart usage they can definitely have their place. You are not wrong about downregulation.


Short of it: Get off your **** people

 

[mujuro]

Found a case study about bromocriptine lowering PTH in a hyperparathyroid patient.

http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2015.BCHVD.7.FRI-231

 

[charlie]

post 106331 ...... but anaerobic exercise still remains the most fool proof way to go about fixing depression in a sustainable way.

 

[haidut]

post 106327

post 81885 So, for people struggling with high serotonin or any of its associated conditions, it seems that dopaminergic drugs may lower serotonin directly in addition to increasing dopamine and lowering prolactin.

Do you think there is any danger in dopaminergic drugs inducing what would effectively be "dopamine resistance" ?

High bursts of dopamine seem to produce that effect, as seen in drug addicts, but if drugs are used to raise dopamine to normal / physiological levels I wonder if there will be any negative effect...

I don't know about resistance but you do need to take a break every once in a while. Dopamine agonists like bromocriptine will downregulate the dopamine "receptors" if used for long time. So, taking a week break every couple of months is probably warranted.

 

[michael94]

post 106356

post 106331 ...... but anaerobic exercise still remains the most fool proof way to go about fixing depression in a sustainable way.

Care to elucidate your criticism?

 

[NathanK]

Good finds here. Thanks.

It appears that dopamine and serotonin are direct antagonists so lowering serotonin may bring up dopamine if there is no dopamine metabolism issues.

I think as far as exercisers "always feeling good" may have as much to do with increased endorphins as much as anything.

Another way to increase dopamine may as well be lowering adrenaline since every molecule of dopamine is synthesized from adrenalin first. If you can lower adrenaline then you may be able to leave more to be channeled to dopamine, iow

 

[michael94]

post 106452

I think as far as exercisers "always feeling good" may have as much to do with increased endorphins as much as anything.

Endorphins are definitely part of it short term, but anaerobic exercise done intelligently ( preferably weight lifting ) increases metabolic rate long term significantly. By intelligently I mean not overdoing it for your fitness level/food intake and focusing on concentric movements.

 

[NathanK]

post 106462

post 106452

I think as far as exercisers "always feeling good" may have as much to do with increased endorphins as much as anything.

Endorphins are definitely part of it short term, but anaerobic exercise done intelligently ( preferably weight lifting ) increases metabolic rate long term significantly. By intelligently I mean not overdoing it for your fitness level/food intake and focusing on concentric movements.

No question about it. Being physically active with some anaerobic exercise plays an important role in overall health. In the least, psychologically and to prevent muscle atrophy.

 

[charlie]

post 106441 Care to elucidate your criticism?

"but anaerobic exercise still remains the most fool proof way to go about fixing depression in a sustainable way.

It's neither "the most" nor "sustainable" and definitely not "fool proof".

 

[aarfai]

I've searched the forum high and wide but what products and/or supplements can one take to raise dopamine levels in order to suppress serotonin? I currently only use BBCAs, cocao and fat soluble vitamins.

 

[Dean]

post 106603 I've searched the forum high and wide but what products and/or supplements can one take to raise dopamine levels in order to suppress serotonin? I currently only use BBCAs, cocao and fat soluble vitamins.

Raising dopamine is a problem I'm wrestling with. Outside of pharmas and what you mentioned, theanine seems to be mentioned a lot. I've been experimenting with Mucuna Pruriens, but I've read it's been shown not to convert very well. Eating a lot of simple sugar seems to give me a dopamine type high. I've been making a concerted effort to raise my caffeine intake as well, which maybe helps? Tianeptine seemed to show some promise for me on that front, but it gave me major constipation.

I just reintroduced cypro two nights ago after having to quit it because it lowered my dopamine too much. I'm hoping all of the above (excluding pharmas) can keep my dopamine up so I can handle cypro this time.