Modifying capsaicin to cross the BBB

[tantric]

Something I read many years ago got stuck in my head. It was by a clandestine chemist who at the end of her post said, "I'm off to aminate capsaicin" . I think it was Wednesday? This is based on the idea that many naturally occuring chemicals in spices can be reductively aminated to make psychedelics.

So, I don't see the amination bit, there's nowhere to go on that except the ketone, and ketones cross over fine. I think the problem is with the hydroxy on the main ring. Generally hydroxy groups on benzyl rings don't cross, thus the difference between ephedrine and amphetamine. You could transform that into a methoxy group, right? Is that even remotely possible?

Note, this is UTTERLY hypothetical. Even if you made it, I wouldn't try it. BUT it might have useful nonnarcotic painfighting effects.

 

[sekio]

Capsacin is already super nonpolar, the reason it doesn't make it to the brain is probably due to protiens that keep it out (e.g. glycoprotiens)

You can't reductively aminate the carbonyl on an amide very well.

 

[serotonin2A]

Anything that increased the ability of capsaicin to get into the brain would probably also increase its bioavailability. That would not be a good thing because activation of TRPV1 throughout the body would potentially produce undesirable side-effects. But it's not clear to me why you would want to activate TRPV1 in the brain. Capsaicin doesn't produce analgesic effects via opioid or cannabinoid mechanisms.

I'm not aware of any evidence that capsaicin doesn't get into the brain. It is already very lipophilic, the free hydroxyl group probably isn't restricting capsaicin from partitioning into the CNS. It should be possible to convert it to the O-acetyl derivative, but I don't see the point. There are many capsaicin analogs that are more drug-like and show better bioavailability and CNS penetration.

 

[Zeds(NCO2CH2CH3)2]

I see no way capsaicin couldn't not enter the brain. Look at it God dam thst GREASY GREASY hydrocarbon amide tail. No groups on the whole molecule are ionized.

My guess is that it's super fast metabolized by COMT in the brain and probably hydrolysizes rapidly ("conjugate base is 3,4 dihydroxy aniline or 3-methoxy 4-hydroxy aniline depending on when hydrolyzed...) Also I would guess the tissue distribution is everywhere and it's difficult to even get a high amt to get around the brain..

Also the more so metabolized demethylated amino catechol or the demethylated catechol alkyl amide is favored in the quinone form and very unstable.. Esp due to that amine it favors quinine methadine type structures.

Zedsdead

 

[ParappaTheRapper]

Well its delicious, helps lose weight, and poteniates oral ROA's, so theres that..