Nitrogen atoms and Psychedelics

[Ego_tripper]

The other day I noticed that all serotonergic psychedelics have at least 1 nitrogen atom that is lost during the metabolism in the body. Metabolites that are still psychoactive seem to have retained their nitrogen atom, while non psychoactive metabolites lost it. I also noticed that it's unique compared to other compounds that aren't psychedelics, like stimulants etc.

I want to know if there is something I'm missing here, I don't know much about nitrogen's role in the brain, but it seems that the "true" psychedelics seem to function because of the nitrogen atom. Seeing as how serotonergic compounds induce a unique altered state of consciousness, I'm wondering about nitrogen's role in consciousness.

I also thought about nitrous oxide, and how the oxygen atom itself isn't psychoactive but it's the combination with the nitrogen atom that makes it alter consciousness.

I'm curious in other's opinions because I can't really find more information about this.

 

[greenmeanies]

there is nothing inherently 'special' or 'psychoactive' about the nitrogen atom; it all depends on bonding characteristics and electron distribution. not so much opinion here, just enzyme mechanics.

our brains have evolved (or been designed) as highly complex machines that use monoamines to transmit information. that is to say, in our gray matter there are lots of enzymes that link up with each other; each of these important enzymes responds to a particular shape of key that fits into the slot. in order to fit into the slot, a molecule must be the correct size (not too big or too small) and have complementary electronic distribution. if the enzyme has a negatively charged area, it will fit a key that has a positively charged area. if the enzyme has a neutral/hydrophobic area, it will fit a key that has a similar neutral area.

since our endogenous ligands (naturally-occurring keys) are monoamines (DA, NE, 5HT), then it would make sense that psychedelics must have this important amine group in order to fit into the lock. at physiological pH, amines are protonated (positively charged) while carboxylic acids are deprotonated (negatively charged). most metabolic pathways for disabling amines is to oxidize them to a carboxylic acid. a negatively charged key will definitely not fit into a lock designed for a positively charged key. note that the pH of spinal fluid is buffered at 7.31

nitrous oxide is somewhat different from other psychedelics, as it is not serotonergic, and i believe is excreted unchanged.

 

[Ego_tripper]

Thank you! This is the information I've been looking for.

 

[Iodjini_dk]

Yeah, pretty much what he said. If you look at the structures of phenethylamine and tryptamine and compare them to neurotransmitters as serotonine and dopamine or amino acids as tryptophan and phenylalanine, it makes good sense that tryps and phens would have some interaction with human enzymes. Tryptamines and phenethylamines are key structures ind the human body.

As for nitrous oxide I dont know. But i think thats a whole different story.

 

[Solipsis]

Well the nitrogen atom doesn't bear specific relevance but amines do. There are monoamines as said above here that form the skeleton of neurotransmitting compounds so it is no wonder that compounds that mimic them also have this group, which is sometimes not a primary amines but a secondary or tertiary. They are called alkaloids. Read this on that subject, I believe it answers your entire question.

This nitrogen containing group is not totally required for psychoactivity by the way. THC and analogues and salvinorin from Salvia Divinorum are among the exceptions. If you look at THC and the endogenous compound anandamide that is related to it, it appears that the nitrogen group is just not the center of metabolism, but with monoamines it is (with the whole MAO system and all).

If there was something else, PM me and I'll either answer it, redirect you to the appropriate thread or reopen this one if need be.

Hope you are satisfied with BL!