Carbonation of Dopamine to make a prodrug?

[Hydroponichronic]

Here's my thought process: Dopamine isn't lipophillic enough to cross the BBB, mostly because of the phenol groups. So, you'd have to add something on there to change that. Key thing is that whatever you added would have to get cleaved after crossing the BBB. Acetylation seems the obvious choice, but I recently got another idea. If one were to protect the nitrogen on DA, could one react the phenols with COCl2 (under dilute conditions) to produce a DA prodrug with a cyclic carbonate group on the ring? The idea being that the carbonate group will hydrolyse easily under biological conditions and will look cooler than diacetyl dopamine. Also, it might actually be active at some receptors.

[Ph0x]

Would run BP through the roof dawg.

[Gun Lover]

Originally Posted by Hydroponichronic

Here's my thought process: Dopamine isn't lipophillic enough to cross the BBB, mostly because of the phenol groups. So, you'd have to add something on there to change that. Key thing is that whatever you added would have to get cleaved after crossing the BBB. Acetylation seems the obvious choice, but I recently got another idea. If one were to protect the nitrogen on DA, could one react the phenols with COCl2 (under dilute conditions) to produce a DA prodrug with a cyclic carbonate group on the ring? The idea being that the carbonate group will hydrolyse easily under biological conditions and will look cooler than diacetyl dopamine. Also, it might actually be active at some receptors.

I rather like the idea, though phosgene isn't easy to come by. It's almost cheating to use that stuff it's so damn useful. Oxalyl chloride, too. Hey, that could also maybe work in your scheme.

The biggest problem is that like chronically abnormal levels of 5-HT, being on that shit could lead to this

I don't know, toying with nonselective dopamimetics is.... just kinda sketchy sounding. MPTP n' shit. Maybe I'm just being a pusscake.

Originally Posted by phox

Would run BP through the roof dawg.

Prolly. I don't know, man. It'd still require like a huge dose and prolly be hydrolyzed to shit in your stomach like instantly.

Fuck I dunno, just earlier I was thinking of a 1,2-diazene amphetamine analogue. If it somehow didn't get protonated to the cation, I think it might yield a neat MDx analogue. Something about the lone pairs and charge distribution makes me have faith.

[reggie_love]

Originally Posted by Gun Lover

I don't know, toying with nonselective dopamimetics is.... just kinda sketchy sounding. MPTP n' shit. Maybe I'm just being a pusscake.

Yeah, I'd worry about this too. It's such a heavy-lifter as NT's go, I'd be afraid to just be like "OKAY MOAR" with its bioavailability across the board.

[JC Denton]

DA prodrug? Lol.

Ever heard of levodopa? It converts to dopamine immediately in the body, and it's available as a supplement at most pharmacies and health stores. People with parkinsons love it.

[Strange Daze]

does levodopa get you high though?
I found this interesting:

[JC Denton]

Originally Posted by Strange Daze

does levodopa get you high though

In my experience it does.

At least, the first time I've taken it. Subsequent tries weren't so successful.

It was one of the most beautiful altered states I've ever experienced in my life. Words can do it little justice, but I felt this perpetual overwhelming feeling of love, it was so intense I felt like I was going to explode. It lasted the entire day and even spilt over into the next. It was like I was looking at the world through rose-tinted glasses. Music sounded incredible and made goosebumps course through my body. I spent the day with my father, and then later in my friend we hiked up this forested mountain to enjoy nature. The whole worlds seemed so incredibly beautiful and I embraced all things with love.

I thought... this must be what Christ consciousness is like.

The problem is, I've so far been unsuccessful in reproducing that high.

All I know is that it must be taken on an empty stomach. A multivitamin/mineral should be alright. Also decaffeinated white tea or some green tea extract may help the conversion process, and prevent breakdown of dopamine into norepinephrine. Any other MAO-B inhibitor should do the job too though.

I do not remember what biological conditions facilitated that high I experienced, but I will do my best to try and figure this out. I still haven't tried increasing the dose, so that is my next experiment. After that, I will try with conjunction with Selegiline. It was similar to phenylethylamine + Selegiline, but much longer lasting.

I found this interesting:

Not really important, but I can add that L-phenylalanine acts as a precursor to L-tyrosine, and also breaks into Phenylethylamine as well. Also epinephrine can be converted to adrenochrome if oxidized.

[L33tz]

Originally Posted by Gun Lover

I rather like the idea, though phosgene isn't easy to come by. It's almost cheating to use that stuff it's so damn useful. Oxalyl chloride, too. Hey, that could also maybe work in your scheme.

The biggest problem is that like chronically abnormal levels of 5-HT, being on that shit could lead to this

I don't know, toying with nonselective dopamimetics is.... just kinda sketchy sounding. MPTP n' shit. Maybe I'm just being a pusscake.




Prolly. I don't know, man. It'd still require like a huge dose and prolly be hydrolyzed to shit in your stomach like instantly.

Fuck I dunno, just earlier I was thinking of a 1,2-diazene amphetamine analogue. If it somehow didn't get protonated to the cation, I think it might yield a neat MDx analogue. Something about the lone pairs and charge distribution makes me have faith.

uh oh

The most common symptom is craving for dopaminergic medication. However other behavioral symptoms can appear independently of craving or co-occur with it.[4] Craving is an intense impulse of the subject to obtain medication even in the absence of symptoms that indicate its intake.[4] To fulfill this need the person will self-administer extra doses. When self administration is not possible aggressive outbursts or the use of strategies such as symptom simulation or bribery to access additional medication can also appear.[4]

Hypomania, manifesting with feelings of euphoria, omnipotence, or grandiosity, are prone to appear in those moments when medication effects are maximum; while dysphoria, characterized by sadness, psychomotor slowing, fatigue or apathy; are typical with DRT withdrawal.[4] Different impulse control disorders have been described including gambling, compulsive shopping, eating disorders and hypersexuality.[4] Behavioral disturbances; most commonly aggressive tendencies are the norm. Psychosis is also common.[4] Another possible symptom is punding, repetition of complex motor behaviors such as collecting or arranging objects.[4]

this sounds familiar

[anunnakiagenda.com]

levodopa? sounds leik a heap of bullshit, especially after you develop tardive dyskinesia

i'm sure you could find safer shit than this, liek alcohol

[iMagiNation]

Originally Posted by anunnakiagenda.com

levodopa? sounds leik a heap of bullshit, especially after you develop tardive dyskinesia

i'm sure you could find safer shit than this, liek alcohol

Gtfo

[anunnakiagenda.com]

I don't like where this thread is going. Going all in for levodopa without considering the substance's potential drawbacks. Tardive dyskenesia may not be reversible, and is quite disabling.

It's not like there's such a thing as the 'perfect drug'. At least know where the drug may take you, whether you like it or not, because you possibly won't like it when it's too late.