8 replies to this topic

[Synaptic-Enthusiastic]

The goal: Increase natural dopamine production and up-regulation of Dopamine Receptors.

The hypothesis: Intake of a Dopamine Antagonist -Metoclopramide- in a very small dose (one tenth of the usual dose) will cause an increased endogenous production of dopamine and up-regulation of the D-Receptors as a response to the blockage for a short period of time ( substance half life:4-6 hours)

Based on: The principle upon which Low Dose Naltrexone works.

Possible applications: Low motivation, ADHD, Asthenia, Depression, Anxiety, Parkinson's like symptoms, any other condition associated with low dopaminergic activity.

Dose: 1mg
1/10th of the normal dose of 10 mg

I am aware that this approach is completely counter-intuitive, for it is stated that:

"Contraindications: "Metoclopramide is contraindicated in pheochromocytoma. It should be used with caution in Parkinson's disease since, as a dopamine antagonist, it may worsen symptoms. Long-term use should be avoided in patients with clinical depression as it may worsen mental state.^[3] Also contraindicated with a suspected bowel obstruction.^[1]
Patients with a history of ADHD, Restless legs syndrome, Hyperprolactinaemia, and Parkinson's disease should be closely monitored when using dopamine antagonists for treatment of emesis. Patients who take antipsychotics are recommended not to take metoclopramide"

However, the very same could be said for the use of Naltrexone in conditions where b-endorphins are lacking, and yet, this somewhat paradoxical mechanism of action seems to work in favor of natural increased production.

Anyone care to add before I try this non-orthodox approach?

[chung_pao]

It's a rational guess that D-receptors would be upregulated in response to antagonism.
However, the duration during which antagonism is active would be very unpleasant...

I think there are more effective targets if your goal is to increase dopamine metabolism, like Tyrosine hydroxyolase (targetted by the CILTEP-stack), hormones (indirect upregulation of tyrosine hydroxylase), fasting, or allosteric modulation of dopamine-receptors.

But please don't be discouraged! For the love of experimentation and strong belief in unexpected outcomes, I'll be following your thread and checking in on the results

But expect that the duration of antagonism might be depressing, like a very strong caffeine crash.

Edited by chung_pao, 30 October 2013 - 05:11 PM.

[lammas2]

This is not a bad idea. I have also dreamed of trying a dopamine antagonist, but it is pretty much impossible for me to obtain prescription drugs.

Anyway, if metoclopramide doesn't work for this purpose, try amisulpride. There is some anecdotal evidence that it does exactly what you want. Some people are also mentioning tolerance that occurs to the antagonistic effects, meaning that after a while it loses it's efficiency. Also, watch out for symptoms of increased prolactin.


Chung_pao, could you shortly describe what is allosteric modulation of dopamine-receptors? How can we achieve this?

Edited by lammas2, 30 October 2013 - 06:09 PM.

[chung_pao]

This is not a bad idea. I have also dreamed of trying a dopamine antagonist, but it is pretty much impossible for me to obtain prescription drugs.

Anyway, if metoclopramide doesn't work for this purpose, try amisulpride. There is some anecdotal evidence that it does exactly what you want. Some people are also mentioning tolerance that occurs to the antagonistic effects, meaning that after a while it loses it's efficiency. Also, watch out for symptoms of increased prolactin.


Chung_pao, could you shortly describe what is allosteric modulation of dopamine-receptors? How can we achieve this?

An allosteric modulator attaches to a natural site at the receptor, normally used for hormones, minerals and other messengers, in order to upregulate/downregulate the receptor.

For example, Testosterone does this to some GABAA receptors in order to make your entire behavior more "cool" and less anxious.
Another example is the racetams; they are AMPAkines, making the AMPA-receptors of the CNS more sensitive to agonists.

The cool thing about this mechanism of action is that it is more likely to be devoid of side-effects and less susceptible to tolerance.
So once more Allosteric modulators become available, we'll be able to produce very strong effects with minimal side-effects and better consistency.

However, right now I don't know of any allosteric modulators of Dopamine receptors, although I haven't looked very much into it.
But I definitely encourage others to check it out and report back if you find anything of this nature.

[kelka]

Dopamine antagonists make me fat and stupid and dopamine agonists make me want to kill people. Tyrosine and taurine behaved as agonists. I have so many memory and brain fog problems at the moment but I really interested in how people respollnd to both these groups and really want too understand my reaction. Incidently both groups gave me muscle pain band worsened my restless leg.

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[Lemon.]

Hi,

The stats seem to be 'Prescription Only', how did you get this if you don't mind me asking please?.
I am very interested, but don't understand why if I went into some random doctor they would write a script.

Any place to get them or something??? ideas please,

Thank You.

Oh wait, the drug you're talking about is a dopamine antagonist (blocks dopamine receptors) ..

oh, no thank you

[celebes]

Naltrexone/Naloxone are inverse agonists not antagonists.

[jacobjerondin]

This is a pretty dang fascinating idea, I;d say it could be quite possible to take something like Metoclopramide at night to avoid the annoying effects of dopamine antagonism. I'd expect that it would improve sleep, and then you could wake up the next day with nice upregulated receptors, in a similar manner to LDN!

 

However, I feel like L-THP extract from corydalis is a much more promising substance for this purpose given its long history of usage and known sleep-inducing effects. It's been in a couple studies to significantly upregulate D2 receptor expression, which is directly connected to motivation and reward! Sounds perfect to me - who's gonna go get some to try? It's easily available online.

[John250]

Could this work with ropinirole as well since the half life is only 6hrs? I just worry that this could cause even more down regulation of dopamine. I know with testosterone even if you take a microdose just one time it can naturally shut down the HPTA so the microdose theory on that would be negated but I’m not sure if neurotransmitters are affected the same ways as hormones.