Increasing dopamine without tolerance or addiction:

Hey guys. I've been hoarding all this information for the past year, and I think it's time I release it to the public. Bromantane and ALCAR are some of the most promising dopaminergics on the market, and this post will explain why.

For those of you confused about dopamine:

To put it simply, it's the motivating neurotransmitter. And this bleeds into things such as optimism, confidence, social interaction, mood, learning etc. It would take 10 posts to go over everything dopamine does, so hopefully you accept the generalization.

Here's a simplified version of the dopamine/ CREB cascade:

Dopamine --> D1 activation --> Adenylate Cyclase --> Cyclic Adenosine Monophosphate (cAMP) production --> Protein Kinase A --> CREB (key factor in learning and memory) --> (ΔFosB --> inhibits C-Fos), Dynorphin (inhibits dopamine release), (Tyrosine Hydroxylase activation --> more dopamine), and so much more.

Your idea of dopamine receptor upregulation may be wrong.

So many things are said to "upregulate dopamine receptors", but what does that truly mean? Well it's not so simple. Usually receptor upregulation just hints at temporarily lowered neurotransmitter causing increased sensitivity to maintain homeostasis. So keep that in mind when discussing Uridine. This source for instance. Or Sulbutiamine. So besides Uridine being GABAergic, that has to be part of Nootropic Depot's motivation to include it in the sleep support stack. Reviews are mixed, but I felt sedated by Uridine Monophosphate.

Cocaine upregulates dopamine receptors. And I'll reference this study later. But basically the transition of CREB to ΔFosB and Dynorphin, leading to a depletion of CREB and dopamine is evidence of tolerance to cocaine. So looking at receptors alone is SIMPLISTIC, especially when you consider the inhibitory role of D2 receptors which people here misconceive to be a good thing. It's almost as simplistic as assuming Tyrosine Hydroxylase upregulation is why Bromantane is so great, which is one of many misconceptions I had in the past. It's the mechanism that makes it great, not just downstream activity.

And by

Has anyone here tried Mebicar/Adaptol (Temgicoluril) or Mexidol (Emoxypine)? Since I have a lifelong GABA deficit, CPTSD, GAB, OCD, emotional dysregulation and ADHD I am aware that after quitting pregabalin I will probably have to find a longterm and safe solution. I tried most of modern western medicine without success and I’ve read about russian anxiolytics. Do you guys have any experience with them? Are they safe longterm (cause they are supposed to be but so did pregabalin :/)

Temgicoluril -

Temgicoluril has an effect on the structure of limbic–reticular activity, particularly on hypothalamus emotional zone, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin, and adrenergic activity. It decreases the brain norepinephrine levels, exerts no effect on the dopaminergic systems, increases brain serotonin levels, and does not elicit cholinolytic action.[5] Temgicoluril purportedly has anti-anxiety (anxiolytic) properties.[5][6][7][8][9] It is also used to aid smoking cessation.[3] In addition, temgicoluril may be useful in the treatment of ADHD symptoms.[10] In contrast with typical anxiolytic medications such as benzodiazepines, temgicoluril is non-habit forming, non-sedating, and does not impair motor function.[6][3] Temgicoluril does not cause mood swings or euphoria, no habituation and addiction, withdrawal syndrome has been observed. Prevents or reduces anxiety, unrest, fear, internal emotional tension and irritability, reduces neuroses and neurotic disorders, heartburns of non-coronary heart disease origin.

Emoxypine -

Its chemical structure resembles that of pyridoxine (a type of vitamin B6).

emoxypine has a wide range of applications in medical practice. It purportedly exercises anxiolytic,[4][5] anti-stress, anti-alcohol, anticonvulsant, nootropic, neuroprotective and anti-inflammatory action.[citation needed] Emoxypine presumably improves cerebral blood circulation, inhibits thrombocyte aggregation, lowers cholesterol levels, has cardioprotective and antiatherosclerotic action.[3] • Emoxypine inhibits free radical[which?] oxidation of biomembrane lipids, reacts to peroxide radicals of lipids primary and hydroxyl radical of peptides

• Increases the activity of antioxidant enzymes, specifically that of superoxide dismutase, responsible for the formation and consumption of lipid peroxides and active oxygen forms
• Inhibits free radicals during the synthesis of prostaglandin catalyzed cyclooxygenase

I don't want to step on anybody's toes here, but the amount of non-dad jokes here in this subreddit really annoys me. First of all, dad jokes CAN be NSFW, it clearly says so in the sub rules. Secondly, it doesn't automatically make it a dad joke if it's from a conversation between you and your child. Most importantly, the jokes that your CHILDREN tell YOU are not dad jokes. The point of a dad joke is that it's so cheesy only a dad who's trying to be funny would make such a joke. That's it. They are stupid plays on words, lame puns and so on. There has to be a clever pun or wordplay for it to be considered a dad joke.

Again, to all the fellow dads, I apologise if I'm sounding too harsh. But I just needed to get it off my chest.

Hello, I am trying to learn more about the GABA-B receptor and VGCC’s.

I used phenibut for 3+ years daily, I quit a year ago. After taking phenibut, no other psychoactive drugs work whatsoever - and yes, that means all of them. MDMA, opiates, stimulants, psychedelics, etc.

Phenibut is a gaba-B agonist and effects VGCC. I’ve done extensive research into the gaba-B effects, and from my research it concludes that stimulating the gaba-B receptor will inhibit other neurotransmitters.

It appears there’s many mechanisms at play that can cause this, but one of which appears to be from the fact that the gaba-B receptor inhibits adynylate cyclase, and that enzyme plays a key role in neurotransmitter release. It also appears calcium channels also play a similar role.

Does anyone else have any more information as to how this works?

Here are some studies below. I quoted the more relevant parts that talk about this.

2 Functions of GABAB Receptors GABAB receptors play a critical role in long-term inhibition of synaptic transmission (Bowery, 1993). In the brain, GABAB receptors are located both pre- and postsynaptically. Activation of presynaptic GABAB receptors inhibits neurotransmitter release from presynaptic terminals (Bowery et al., 1980; Bowery, 1993). Presynaptically, GABAB autoreceptors have been reported to control the release of GABA, whereas GABAB heteroreceptors regulate the release of glutamate, noradrenalin, dopamine, 5-hydroxytryptamine, substance P, cholecystokinin, and somatostain (Kaupmann et al., 1997)”

“GABAB receptors (GABABRs) regulate the excitability of most neurons in the central nervous system by modulating the activity of enzymes and ion channels. In the sustained presence of the neurotransmitter γ-aminobutyric acid, GABABRs exhibit a time-dependent decrease in the receptor response—a phenomenon referred to as homologous desensitization. Desensitization prevents excessive receptor influences on neuronal activity.”

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/gabab-receptor

https://www.cell.com/neuron/fulltext/S0896-6273(00)80381-5#back-BIB27

“GABAB receptors are G protein-coupled receptors that mediate slow and prolonged inhibitory action, via activation of Gαi/o-type proteins. GABAB receptors mediate their inhibitory action through activating inwardly rectifying K+ channels, inactivating voltage-gated Ca2+ channels, and inhibiting adenylate cyclase.”

“whereas the metabotropic GABAB receptor pr

Do your worst!

I'm surprised it hasn't decade.

For context I'm a Refuse Driver (Garbage man) & today I was on food waste. After I'd tipped I was checking the wagon for any defects when I spotted a lone pea balanced on the lifts.

I said "hey look, an escaPEA"

No one near me but it didn't half make me laugh for a good hour or so!

Edit: I can't believe how much this has blown up. Thank you everyone I've had a blast reading through the replies 😂

It really does, I swear!

Buenosdillas

They’re on standbi

Pilot on me!!

Nothing, he was gladiator.

Dad jokes are supposed to be jokes you can tell a kid and they will understand it and find it funny.

This sub is mostly just NSFW puns now.

If it needs a NSFW tag it's not a dad joke. There should just be a NSFW puns subreddit for that.

Edit* I'm not replying any longer and turning off notifications but to all those that say "no one cares", there sure are a lot of you arguing about it. Maybe I'm wrong but you people don't need to be rude about it. If you really don't care, don't comment.

When I got home, they were still there.

What did 0 say to 8 ?

" Nice Belt "

So What did 3 say to 8 ?

" Hey, you two stop making out "

I won't be doing that today!

[Removed]

You take away their little brooms

This morning, my 4 year old daughter.

Daughter: I'm hungry

Me: nerves building, smile widening

Me: Hi hungry, I'm dad.

She had no idea what was going on but I finally did it.

Thank you all for listening.

There hasn't been a post all year!

Why

It’s pronounced “Noel.”

After all his first name is No-vac

What, then, is Chinese rap?

Edit:

Notable mentions from the comments:

• Spanish/Swedish/Swiss/Serbian hits

• French/Finnish art

• Country/Canadian rap

• Chinese/Country/Canadian rock

• Turkish/Tunisian/Taiwanese rap

There hasn't been a single post this year!

(Happy 2022 from New Zealand)

Nothing, it just waved

Him: I can explain everything!

(It's his best joke yet I think)

Bob

So that I could frequently say, "I am going to walk 5 miles now."

Edit: My most popular post on Reddit! 😀 Thank you for the awards.

Just to clarify, 12345678

Me grabbing a soda from my (what I thought was) half full 12pk...

Notices there's only 2;

Me: "Awe man... This is a damn bird box!" Her: "What the hell does that mean?!" Me: (Pulls both cans out & shows them to her) "It's only got Toucans."

I'm not ashamed to admit the look on her face was glorious.

Increasing dopamine without tolerance or addiction:

Hey guys. I've been hoarding all this information for the past year, and I think it's time I release it to the public. Bromantane and ALCAR are the most promising dopaminergics on the market, and this post will explain why.

For those of you confused about dopamine:

To put it simply, it's the motivating neurotransmitter. And this bleeds into things such as optimism, confidence, social interaction, mood, learning etc. It would take 10 posts to go over everything dopamine does, so hopefully you accept the generalization.

Here's a simplified version of the dopamine/ CREB cascade:

Dopamine --> D1 activation --> Adenylate Cyclase --> Cyclic Adenosine Monophosphate (cAMP) production --> Protein Kinase A --> CREB (key factor in learning and memory) --> (ΔFosB --> inhibits C-Fos), Dynorphin (inhibits dopamine release), (Tyrosine Hydroxylase activation --> more dopamine), and so much more.

Your idea of dopamine receptor upregulation may be wrong.

So many things are said to "upregulate dopamine receptors", but what does that truly mean? Well it's not so simple. Usually receptor upregulation just hints at temporarily lowered neurotransmitter causing increased sensitivity to maintain homeostasis. So keep that in mind when discussing Uridine. This source for instance. Or Sulbutiamine. So besides Uridine being GABAergic, that has to be part of Nootropic Depot's motivation to include it in the sleep support stack. Reviews are mixed, but I felt sedated by Uridine Monophosphate.

Cocaine upregulates dopamine receptors. And I'll reference this study later. But basically the transition of CREB to ΔFosB and Dynorphin, leading to a depletion of CREB and dopamine is evidence of tolerance to cocaine. So looking at receptors alone is SIMPLISTIC, especially when you consider the inhibitory role of D2 receptors which people here misconceive to be a good thing. It's almost as simplistic as assuming Tyrosine Hydroxylase upregulation is why Bromantane is so great, which is one of many misconceptions I had when I wrote [this](https://www.reddit.com/r/Nootropics/comments/jhos16/the_resolution_to_dopamine_do