Histamine as a basis for novel-ish psychedelics

[Ham-milton]

I was doing some playing around with chemdraw today thinking about the potential to use histamine as a backbone for novelish, "not quite tryptamine" indole-ish psychedelics, but as fair as I can tell, no one has ever tried this out.

In my searching, I actually found a quote from Shulgin at MDMA.net:

Phenethylamines and tryptamines are the two basic building blocks of psychedelics, by boosting their neurotransmitter counterparts in the brain. Are you researching any newly-found substances that can stimulate other, similar transmitters?

S: The brain neurotransmitters that are most closely related to phenethylamine and to tryptamine are dopamine and serotonin respectively. I am not sure that I would use the word "boosting" as a description however! These brain neurotransmitters are clearly involved in the action of the psychedelic drugs, but the interrelationships are not as simple nor as well understood and the neurologists would have you believe. There is a chemically related natural neurological agent that has the potential of parallel chemistry; this is the material histamine. With a black-board and a good supply of chalk, one could parallel the chemistry of both the phenethylamines and the tryptamines and draw a host of compounds that might possibly be psychoactive. But this is a theoretical world without any present known promise, and must wait for some future enthusiast to champion it.

Though I suppose it's probably been thought of before, it still felt good to come up with something on my own and then realize that Shulgin already had the idea.

Does anyone here know if this is something that'd be worth pursuing, or has already been pursued (and presumably abandoned when they failed?).

 

[LuxEtVeritas]

HiHKaL
...doesn't ring right, LOL

i doubt it...

 

[Ham-milton]

Doubt that psychedelics based on histamine could be created or that they'd be as accepted as the tryptamines and phenylethylamines?

that would make for a hideous title, though.

I would assume that something similar to this would have potential:

 

[johanneschimpo]

Isn't that N+ is going to kill all activity... Resolving the + charge would have a large effect on the ring structure, killing aromaticity, if it has it, or opening the ring.
Doesn't look like its going to work well, but I wouldn't necessarily take my word as gospel on this subject.

 

[Ham-milton]

No, you're absolutely right. that structure wasn't all that well thought through. I'm not positive that the benzene is properly located.

 

[kidamnesiac]

i think it would be better with purines if your doing analogs

If I know, which I don't, I think the activity would be in messing with the alkyl chain on histamine, or at least making oxazoles or other small ring rearrangements.

 

[Beenhead]

Isn't that N+ is going to kill all activity... Resolving the + charge would have a large effect on the ring structure, killing aromaticity, if it has it, or opening the ring.
Doesn't look like its going to work well, but I wouldn't necessarily take my word as gospel on this subject.

IS that why Propylhexadrine looses much dopaminergic activity because it is nonaromatic? How does this play a role in Binding affinity

 

[johanneschimpo]

Apparently. The double bonds/aromaticity are all that separate it from methamphetamine. It would be interesting to know what happened if you didn't make it aromatic, but instead just added 1 double bond, making it a cyclohexene ring. I wonder if that would add some activity compared to the saturated ring. I've never formally approached the subject though, so not I'm sure on any of the specifics.

Anyone?