11 replies to this topic

[Curiouser]

Hey brilliant minds,

I'm looking for some dopamine agonism that does NOT include norepinephrine agonism. And I want to do it legally, without a prescription (so no pramipexole, etc).

Any ideas?

PS Yeah, I know that I misspelled "norepinephrine" in the title. Bullocks.

Edited by Curiouser, 25 November 2010 - 04:25 PM.

[Ark]

I'd suggest looking into selegiline P-5-P & Taurine, or 2-aminoethanesulfonic acid.

[Curiouser]

I'd suggest looking into selegiline P-5-P & Taurine, or 2-aminoethanesulfonic acid.

Selegiline: no-go, MAOI causes norepinephrine upregulation alongside dopaminergic upregulation.
P-5-P: no-go, converts L-DOPA to dopamine... but then dopamine is converted to norepinephrine.
Taurine: this might work. appears to actually decrease NE release, which is optimal. thx for suggestion-- will look into it!

Anyone else have another other suggestions?

Edited by Curiouser, 25 November 2010 - 05:16 PM.

[Animal]

I'd suggest looking into selegiline P-5-P & Taurine, or 2-aminoethanesulfonic acid.

Selegiline: no-go, MAOI causes norepinephrine upregulation alongside dopaminergic upregulation.

It's exclusively an MAO-B inhibitor, which only catabolises dopamine. But you said no pharmaceuticals, so it's irrelevant anyway.

[ritch]

what about l-tyrosine? 3 grams empty stomach twice a day. Makes noops and stims more effective as well.

[Curiouser]

It's exclusively an MAO-B inhibitor, which only catabolises dopamine. But you said no pharmaceuticals, so it's irrelevant anyway.

Good point. And since I know you're skilled at this, what are your thoughts on taurine? Do you think it would get me to where I want to go? Specifically, I'm trying to target the cerebro-cerebellar circuit, where the Purkinje fibers upregulate dopamine at the mPFC. But at the same time, I would prefer to downregulate norepinephrine... or at least hold it steady.

Edited by Curiouser, 26 November 2010 - 03:58 AM.

[Curiouser]

what about l-tyrosine? 3 grams empty stomach twice a day. Makes noops and stims more effective as well.

Sadly, no. All that dopamine is then catabolized into norepinephrine! However, as Animal pointed out, MAOI-B wouldn't have this effect since it inhibits catabolism of dopamine.

[Animal]

It's exclusively an MAO-B inhibitor, which only catabolises dopamine. But you said no pharmaceuticals, so it's irrelevant anyway.

Good point. And since I know you're skilled at this, what are your thoughts on taurine? Do you think it would get me to where I want to go? Specifically, I'm trying to target the cerebro-cerebellar circuit, where the Purkinje fibers upregulate dopamine at the mPFC. But at the same time, I would prefer to downregulate norepinephrine... or at least hold it steady.

What are the symptoms you are trying to alleviate that lead you to believe that this specific mechanism of action will be helpful?

[Curiouser]

It's exclusively an MAO-B inhibitor, which only catabolises dopamine. But you said no pharmaceuticals, so it's irrelevant anyway.

Good point. And since I know you're skilled at this, what are your thoughts on taurine? Do you think it would get me to where I want to go? Specifically, I'm trying to target the cerebro-cerebellar circuit, where the Purkinje fibers upregulate dopamine at the mPFC. But at the same time, I would prefer to downregulate norepinephrine... or at least hold it steady.

What are the symptoms you are trying to alleviate that lead you to believe that this specific mechanism of action will be helpful?

Emotional and behavioral disinhibtion. During highly charged situations, I've long had the tendency to tell myself to "stop"... and yet I keep going. Then I don't understand why I did something that I had told myself not to do. Recently, I read a paper about mice with k.o'd cerebro-cerebellar tracts that appear to do the same thing. I had other similarities to the mice. In particular, they were unable to generate DA at the mPFC. I have long had the subjective feeling that I'm low in DA. I also have signs of DA downregulation such as going years at a time without dreaming, and talking extensively in my sleep with no memory of it the next day. However I'm very, very sensitive to NE, and could probably do with less of that, not more.

Edited by Curiouser, 27 November 2010 - 12:44 AM.

[jadamgo]

Targeting complex behaviors such as social expression of emotion can certainly be done with activation of the prefrontal cortex, though it's difficult to target dopamine agonism so that it specifically activates the PFC. Most agonists will affect other systems, such as reward and movement.

Since the behavior appears when you're under stress, you could also consider anxiolysis instead of stimulating the PFC. Luckily, selegiline can both stimulate the PFC and provide some anxiolysis, and it can pretty easily be gotten without a prescription. Supplementation with phenylalanine may increase the anxiolytic effect of selegiline, but some people have reported issues with tolerance. So you may want to save it for when you know you'll be entering a charged situation. The conversion from PLA to tyrosine is slow and inefficient, so don't expect PLA supplementation to increase norepinephrine. There are just too many links in the chain between PLA and NE.

Theanine and picamilon are more options to increase DA and provide anxiolysis.

I can think of a good pharmaceutical that would target the exact symptom you're talking about, by agonizing DA without agonizing NE, but you said you weren't interested in pharmaceuticals... So I guess I won't mention how perfect dexmethylphenidate could be for you.

I suggest that you also consider dopaminergics that have some effects on NE, because you could just antagonize the NE.

[Curiouser]

Targeting complex behaviors... you could just antagonize the NE.

Great reply, jada! Thanks so much for your help!

I think I'd prefer to stay away from selegiline and dexmeth b/c I'm already too "speedy" by nature. I had been eyeing rasagiline, though (I've suddenly decided that anything you can get from ADC doesn't count as illegal, ha ha).

If you were in my position, what would you do? Again, I'm speedy by nature but can get quite depressed when I feel DA levels go down. So I'm looking for something powerful enough to hold DA up without pushing NE way, way up.

Also, what would you use to antagonize NE? The only NE antagonist I've tried is clonidine. It's efficacious, but can be rather stultifying, so I'd rather take it prn as opposed to qd.

Edited by Curiouser, 30 November 2010 - 02:55 AM.

[jadamgo]

Targeting complex behaviors... you could just antagonize the NE.

Great reply, jada! Thanks so much for your help!

I think I'd prefer to stay away from selegiline and dexmeth b/c I'm already too "speedy" by nature. I had been eyeing rasagiline, though (I've suddenly decided that anything you can get from ADC doesn't count as illegal, ha ha).

If you were in my position, what would you do? Again, I'm speedy by nature but can get quite depressed when I feel DA levels go down. So I'm looking for something powerful enough to hold DA up without pushing NE way, way up.

Also, what would you use to antagonize NE? The only NE antagonist I've tried is clonidine. It's efficacious, but can be rather stultifying, so I'd rather take it prn as opposed to qd.

If it was me, then I'd keep some clonidine and some DLPA around to use prn for stressful situations that you can see coming ahead of time. I'd also continue looking into rasagiline.

For daily use, I'd come up with a stack of supplements/herbs. This stack would reduce anxiety and increase PFC activity. I'm not very experienced with anxiolytics, and I get all the PFC enhancement I need from methylphenidate. But some components you could look into are theanine, picamilon (note how picamilon's effects change depending on dosage), bacopa, ashwagandha, green tea extract, lion's mane, chamomile, lemon balm, lavender, brahmi, ALCAR/ALA, N-acetyl cysteine, Rhodiola rosea, korean ginseng, and eleuthero. If you're ambitious, you could try mucuna pruriens, which contains levodopa -- but take it WITH the green tea extract, because one of those polyphenols acts as a peripheral DOPA decarboxylase inhibitor.

Wow, that's a lot. I am not specifically recommending any of these to you, because I am not personally familiar with any of them except picamilon, chamomile, and green tea extract. But those are all things you could look into for coming up with a good stack.

Before I started taking the stack, I would post it on the "regimens" section of the forum and ask for suggestions to improve it. THEN I would buy the components and start taking them, adding one component every 3-5 days so that I could recognize if one of them was causing side effects.