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Anyone tried apomorphine? (122x increase in NGF, 3x GDNF, dopamine repair, not an opioid)

apomorphine ngf gdnf dopamine

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#1 gintrux

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Posted 26 July 2020 - 10:56 AM


Has anyone tried apomorphine or looked deeper into its potential as a behaviour altering substance? I wonder whether it could improve motivation and increase dominant personality traits based on the assumption that dopamine plays a significant role in those and that apomorphine is a dopamine agonist.

https://en.wikipedia...iki/Apomorphine

Apomorphine was also used as a private treatment of heroin addiction, a purpose for which it was championed by the author William S. Burroughs. Burroughs and others claimed that it was a "metabolic regulator" with a restorative dimension to a damaged or dysfunctional dopaminergic system. There is more than enough anecdotal evidence to suggest that this offers a plausible route to an abstinence-based model; however, no clinical trials have ever tested this hypothesis.

 

Apomorphine also reduces the breakdown of dopamine in the brain (though it inhibits its synthesis as well).[19][20]

It is a powerful upregulator of certain neural growth factors,[21] in particular NGF and BDNFepigenetic downregulation of which has been associated with addictive behaviour in rats.[22][23]

 

We next examined the time course of NGF secretion, as well as that of BDNF and GDNF, by mouse astrocytes incubated with 88 mM apomorphine (Fig. 2). The NGF content in the culture medium was not affected by apomorphine up to 2 h, but increased rapidly to 20-fold of the control at 4 h, 50-fold at 6 h, and 122-fold (1681 pg/ml, P , 0.001, Student’s t-test) at 24 h (Fig. 2A). The BDNF content was not significantly altered by apomorphine, compared with the control value throughout the period of time examined (Fig. 2B). The GDNF content remained at the control level up to 6 h but increased significantly to 1.8-fold (42 pg/ml, P , 0.005, Student’s t-test) by apomorphine at 24 h (Fig. 2C).

...

Expression of GDNF mRNA increased with time, reaching the maximum level at 15 h (2.9-fold of the control) after the addition of apomorphine before subsequent decrement at 24 h (Fig. 4)

onsl7mhzr6d51.png?width=708&format=png&a

https://libgen.lc/sc...2&downloadname=

https://pubmed.ncbi....h.gov/10872797/

 

Despite morphine in its name, it has no binding on opioid receptors by the way. It does have some downsides:

It is a potent emetic and should not be administered without an antiemetic such as domperidone. The emetic properties of apomorphine are exploited in veterinary medicine to induce therapeutic emesis in canines that have recently ingested toxic or foreign substances.

 

 

A. N. Ernst then discovered in 1965 that apomorphine was a powerful stimulant of dopamine receptors.[42] This, along with the use of sublingual apomorphine tablets, led to a renewed interest in the use of apomorphine as a treatment for alcoholism. A series of studies of non-emetic apomorphine in the treatment of alcoholism were published, with mostly positive results.

 

As the drug is known to be reasonably safe for use in humans, it is a viable target for repurposing.

Apomorphine has been researched as a possible treatment for erectile dysfunction and female hypoactive sexual desire disorder, though the arousal effects were found not to be reliable enough

 

Apomorphine is reported to be an inhibitor of amyloid beta protein (Aβ) fiber formation, whose presence is a hallmark of Alzheimer's disease (AD), and a potential therapeutic under the amyloid hypothesis

Some clinic seems to be offering apomorphine for erectile dysfunction and claims it also improves motivation of their patients

https://innovativeme...-and-motivation

 


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#2 Targz

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Posted 27 July 2020 - 02:54 AM

It should also be noted that apomorphine has extreme side effects and can cause DAWS (dopamine agonist withdrawal syndrome). It also agonizes presynaptic autoreceptors, inhibiting dopamine release, and has neuroleptic effects in rodents. It is also not only a sedative, but a strong emetic. It will not "increase dominant personality traits" as you seek. Apomorphine can also really screw with your prolactin levels. Dopamine agonists are not a good idea to mess with.



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#3 gintrux

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Posted 27 July 2020 - 09:25 AM

Hmm, I'm drawing personal conclusions about safety based on the fact that it's used in the market for erectile dysfunction. It's not a recommendation for another person, but for me personally, that would be safe enough just to try it.

 

I'm wondering whether it could have a sort of build-up effect, where you would take it for a while, it would restore/rebalance dopamine system, you would stop taking and gains would last for some time. Something you would use maybe once a week or who knows. It was/is used as a treatment for addictions, where I understood that a single dosage of apomorphine repaired dopamine system enough so that people don't want an opioid/alcohol anymore. So I mean this could give lasting positive gains on the brain in my view.

 

 

Also interested whether it could have some positive effect for anhedonia.

 

In male rats, the dopamine agonist apomorphine (APO) generally facilitates copulatory behavior.

https://pubmed.ncbi....h.gov/22405778/

 

 

 

I'm willing to try on myself, but the first step is to calculate the dosage to maximize NGF like in that study link, can you help me with that?


Edited by gintrux, 27 July 2020 - 09:28 AM.


#4 Targz

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Posted 28 July 2020 - 03:20 AM

Hmm, I'm drawing personal conclusions about safety based on the fact that it's used in the market for erectile dysfunction. It's not a recommendation for another person, but for me personally, that would be safe enough just to try it.

 

I'm wondering whether it could have a sort of build-up effect, where you would take it for a while, it would restore/rebalance dopamine system, you would stop taking and gains would last for some time. Something you would use maybe once a week or who knows. It was/is used as a treatment for addictions, where I understood that a single dosage of apomorphine repaired dopamine system enough so that people don't want an opioid/alcohol anymore. So I mean this could give lasting positive gains on the brain in my view.

 

 

Also interested whether it could have some positive effect for anhedonia.

 

https://pubmed.ncbi....h.gov/22405778/

 

 

 

I'm willing to try on myself, but the first step is to calculate the dosage to maximize NGF like in that study link, can you help me with that?

 

It's a potent emetic, meaning it's going to make you nauseous and want to throw up. It's also a presynaptic dopamine agonist so it's going to sedate you. People that have tried apomorphine have a generally negative disposition towards it. It's not something fun to experiment with for sure.



#5 Targz

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Posted 28 July 2020 - 03:27 AM

If you're looking for a powerful upregulation of NGF and other neurotrophic factors through dopamine signalling, I'd recommend selegiline.



#6 gintrux

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Posted 29 July 2020 - 08:10 PM

I'm willing to gamble, fuck it.

 

Started to look for a vendor. Found a sexshop selling it lol

https://vieproducts....ine-sublingual/

 

Their products are pretty high end!  MORE PLEASE® MULTIORGASM PILL, PINK AGAIN® ANAL BLEACH, PERIOD BLOCKER®

 

So it looks like high-end tomorrow's nootropics will be bought from... a sex shop. They didn't write the dosage though, so while I'm waiting for their response, I'm still looking for vendors. Who can help me find? Preferably in Europe.



#7 ibtisam_midlet

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Posted 21 August 2020 - 10:50 PM

based on wikipedia and my calculation of its affinity it a D4/D3 agonist what will cause wide range of effect included but not limited in:

 

because of D4:

Novelty seeking (increases the propensity for exploring to select a novel choice over familiar one (eg, human example in this is relationship cheating))

increase working memory performance and fear

 

because of D3:

increase reward for: shopping, gambling, eating, sex, drug seeking behaviors, Risk-Taking , impulsivity

Stimulation of yawning

anti-empathy effect

anti-restless leg syndrome

vomiting



#8 Automail

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Posted 14 September 2020 - 06:12 AM

"Burroughs and others claimed that it was a "metabolic regulator" with a restorative dimension to a damaged or dysfunctional dopaminergic system." 

I mean, yeah, that's what GDNF does.



#9 gintrux

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Posted 14 September 2020 - 02:16 PM

Don’t know if it’s of any relevance, but I read ibogaine supposedly raises GDNF after the trip by orders of magnitude, however after my iboga ta 1g trip, I did NOT feel any dopaminergic repair, in fact developed a sort of avolition like “laziness”. Things became quite more difficult to do, feeling practically no motivation.
So I wouldn’t categorize GDNF as inherently causing guaranteed repair of something

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#10 Targz

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Posted 14 September 2020 - 08:54 PM

Just please do not take dopamine agonists. They're almost guaranteed to make you addicted to sex and gambling and make it harder to resist cravings and work on long term goals. The behavioral effects are universally considered side effects, and the main effects are supposed to be increasing trophic factors in the nigrostriatal movement pathway to prevent movement disorders in parkinson's in severely damaged dopamine neurons, with greater than 50% loss of neurons in the pathway. This shit will not improve your cognition. It doesn't improve enjoyment of things either, just cravings. It's basically a pro-addiction anti-empathy pill.







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