Trace amines

[Tsukasa]

So I have a few questions, since I can't find enough info, because it's rather scarce.

First about Phenylethylamine: Does PEA have any other actions besides increasing the release of acetylcholine, supression of GABA-b receptors, and indirect activation of dopamine autoreceptors? Does the newly synthesized dopamine have any selective affinity for any DA receptors? What interaction would PEA have with say... phenibut, baclofen, or GHB? anti-cholinergics? tobacco?

And what about the mechanism of action of other trace amines like tryptamine, tyramine, octopamine, and 3-iodothyronamine, as neuotransmitters. I know they all bind to the TAAR receptors, but what other actions do they have?

Is indolamine, and endogenous N,N-DMT, NMT, and 5-MeO-DMT are only found in trace amounts in the body, and they are "amines", so would it be reasonable to assume they are TA's?

And finally, how does the TAAR receptor work? Does it have effects similiar to existing receptors in the body or does it have a completely different function?

 

[Hammilton]

bstract

While the endogenous hallucinogens, N,N-dimethyltryptamine, 5-hydroxy-N,N-dimethyl-tryptamine and 5-methoxy-N,N-dimethyltryptamine, have been acknowledged as naturally occurring components of the mammalian body for decades, their biological function remains as elusive now as it was at the time of their discovery. The recent discovery of the trace amine associated receptors and the activity of DMT and other hallucinogenic compounds at these receptor sites leads to the hypothesis that the endogenous hallucinogens act as neurotransmitters of a subclass of these trace amine receptors. Additionally, while activity at the serotonin 5-HT2A receptor has been proposed as being responsible for the hallucinogenic affects of administered hallucinogens, in their natural setting the 5-HT2A receptor may not interact with the endogenous hallucinogens at all. Additionally 5-HT2A agonist activity is unable to account for the visual altering effects of many of the administered hallucinogens; these effects may be mediated by one of the endogenous hallucinogen trace amine receptors rather than the serotonin 5-HT2A receptor. Therefore, activity at the trace amine receptors, in addition to serotonin receptors, may play a large role in the sensory altering effects of administered hallucinogens and the trace amine receptors along with their endogenous hallucinogen ligands may serve an endogenous role in mediating sensory perception in the mammalian central nervous system. Thus the theory proposed states that these compounds act as true endogenous hallucinogenic transmitters acting in regions of the central nervous system involved in sensory perception.

Their role is complicated, and the different TAAR receptors seem to have very distinct roles. Agonists at some are apparently effective anxiolytics, and IIRC, some play an important role in parkinson's.

 

[Tsukasa]

So 5-meo-dmt, dmt, and nmt, are known bind to 5-HT2A and TAAR receptors? It also says the TAAR receptor may be responsible for it's visually altering effects. Interesting.
I've also read somewhere that DMT does something with the sigma receptors. Other psychadelics such as DXM bind to these same enigmatic sites, so that could possibly play a role in their hallucinogenic properties too.

Good info, thanks. That answers my third paragraph of questions.

 

[Riemann Zeta]

That wacky sigma receptor...after all this time, we still have little clear idea what it does, at neither the neurochemical nor a psychical level. Here's a link to a post I made a while ago about that poster at SfN 2008 talking about DMT and the sigma receptor.

http://www.bluelight.ru/vb/showthread.php?t=410139&highlight=DMT,+sigma+receptor

And here is a link to the paper in Med. Hypotheses about the idea that DMT, beta-phenethylamine and low doses of dextroamphetamine could serve as anxiolytics by hitting various trace amine receptors.

http://www.journals.elsevierhealth.com/periodicals/ymehy/article/PIIS0306987704005870/abstract

 

[Temeraroius]

Not sure if this helps but I know tobacco does act as an MAOI to a certain extent (not sure if its B or A). I am also pretty sure that pretty much all tryptamines and PEA based drugs are metabolized by MAO (sorry no source on this other than wiki). I would think that the whole TAAR DMT assumption is reasonable. I am also very interested in what the true purpose of the TAAR is (and also what agonism/antagonism causes).

 

[Tsukasa]

Riemann - Yea, that's probably were I read it from. I posted in that thread. Oh, and have you heard of the recent discovery of a third sigma receptor?

Temeraroius - Tobacco contains betacarbolines like harmaline, which I think are primarily MAOb, though i'm not sure if it's just B, and not also A. I know their are studies showing tobacco smokers have much lower levels of MAO in their brains, but either they weren't too specific or I just don't recall. Too lazy to check at the moment though lol.

 

[Hammilton]

No, they're MAO-A inhibitors with little or no B affinity. Any inhibition of B-type enzymes would have to be the result of metabolites.

 

[Tsukasa]

^ http://en.wikipedia.org/wiki/Harmine
http://en.wikipedia.org/wiki/Harmaline

My bad, you're right.

Don't want to get too off topic, but are their any naturally occuring MAOb inhibitors?

 

[Hammilton]

If there are, they're either very unknown or they're not viable (present at too low of levels, toxic effects) because they haven't shown up at all.

My hope was for a naturally available MAO-B Inhibitor because that would have been a lot easier to use for PEA experiments than selegiline.

 

[wreckhead]

I say just go with selegiline. I order it online for about $4 for 10 x 5mg, and even when the company wrote the name of the drug on the package, all I had to do was pay a customs charge. Prescription-only stuff isn't illegal to buy in small amounts, as far as I know. Even if it is, it really doesn't seem enforced. Of course benzos and other illegals are different.

 

[Tsukasa]

Yea, i'm aware that i can buy selegiline off certain IOP's. I might get some if I decide to purchase some PEA.

So theirs really no natural selective mao-b inhibitors? Only one I know of is gingko biloba which inhibits both A and B pretty much equally, but it's not potent enough, and my tolerance to it is rather high. Not selective either.