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Tryptamine Serotonin Releasing Agents?

(zonk)

(zonk)

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I can totally see how AMT/AET are SRAs but Wiki lists Tryptamine and 5-meo-T as SRAs as well, however if couldn't find much info expounding upon that. Can anyone tell me more, like how they would fare as SRAs with MAOI. Yes I know how dangerous that sounds but I really do want to know if they are strong enough SRAs for it to be dangerous etc...
 
Serotonin releasers combined with a MAOI is a recipe for disaster. Especially when the serotonin-releasing drugs are broken down by MAOI too (this is one of the reasons that straight tryptamine is useless as a psychedelc)

Do you mean drugs that reverse the serotonin transporter, or drugs that act via agonism of 5-HT1a? Or something else entirely?
 
i mean releasing agents that act in similar ways to serotogenic amphetamines like MDMA etc...
 
yes i'm well aware of the dangers as i've already stated which is why i'm trying to get an idea of how dangerous this actually would be meaning are these actually SRAs to any substantial degree
 
what about regular tryptamine and 5-meo-T(mexamine). Let's say... w/o MAOI, either of those were to be injected directly into the brain, would their action be similar to, greater or less than that of mdma/amt etc... and not even really by a dose to dose basis but an overall effect. would the SRA effect be greater or less than their 5-HT2 agonisms if those 2 basic tryptamines are infact SRAs?
 
One isomer of AMT appears to mediate the hallucinogenic activity, the other the entactogenic activity. I have often wondered if the resolution would lead to 2, totally different compounds. The chemistry is almost, but not quite trivial.

Obviously I cannot cite reference since the papers also have the chemistry in them, which isn't allowed.
 
DMT and other dialkylated ring-unsubstituted tryptamines are in fact SERT substrates, which is to say serotonin releasers.

http://bitnest.ca/external.php?id=%1F%3D5J%19%0D%1F%1EEFW-d%0EVFH%5ER%04JHpcb%15Ua -- fun fact: none other than Alexander Shulgin co-authored this paper.

How this can be reconciled with the known safety of the ayahuasca combination I'm not exactly sure, but I imagine it has to do with the relative ease of breakdown of DMT by other pathways resp. the relative metabolic stability of MDMA, PMA et al. It may also be related to DMT's simultaneous inhibition of VMAT2 which prevents the "ordinary" release of serotonin but not the "extraordinary" release caused by SERT reversal.

(To my knowledge, the 4-OH tryptamines have no SERT activity, the 5-MeO tryptamines are all reuptake inhibitors but not releasers)

One isomer of AMT appears to mediate the hallucinogenic activity, the other the entactogenic activity. I have often wondered if the resolution would lead to 2, totally different compounds. The chemistry is almost, but not quite trivial.
Click to expand...

Iiiiiinteresting!
 
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I would be prepared to bet that (-)AMT is going to be VERY like MDMA indeed. There are some really nice practical aspects to this as well...
 
Perhaps this study would be of interest to you.

Of the tryptamine derivatives (Table 3 and Fig. 1), AMT had
the strongest monoamine-releasing activity, which was approximately
the same as that of methamphetamine, a known
monoamine releaser. 5-MeO-AMT was next in level of activity,
while other derivatives, such as DPT, 5-MeO-DIPT, 5-MeOMIPT,
and 5-MeO-DALT, showed only slight monoaminereleasing
activity.
Click to expand...

I can't really speak to your actual question though
 
DMT and other dialkylated ring-unsubstituted tryptamines are in fact SERT substrates, which is to say serotonin releasers.
Click to expand...

I don't think that's completely right- emphasis on think! I know many are SERT substrates, but does this always cause 5HT release? I would think no, but I'm not positive.
 
sekio said:
Serotonin releasers combined with a MAOI is a recipe for disaster. Especially when the serotonin-releasing drugs are broken down by MAOI too (this is one of the reasons that straight tryptamine is useless as a psychedelc)
Click to expand...

It was only quite recently infact that I learned alot of drugs are serotonin releasing agents that are also MAOIs. I used to think that p-MTA was somehow a freak compound that it did both but there are plenty of other examples as well. E.g. p-chloroamp as well as p-bromoamp are both good MAOIs that are also 5HT releasers. Etryptamine is another great example of a 5HT releaser that also inhibits MAO.
 
i dont think the p-Haloamps are very strong MAOIs compared with MTA, that sulfur changes things quite a bit. Just plain amphetamine is a slight MAOI as well i guess anything metabolized by a certain enzyme will inhibit it a bit. Amp is also a monoamine releaser of 5ht but compared with p-sub/MD compounds it's pretty insignifigant
 
Hammilton said:
I don't think that's completely right- emphasis on think! I know many are SERT substrates, but does this always cause 5HT release? I would think no, but I'm not positive.
Click to expand...

I think you're right. SERT substrates include anything that binds to the transporter including serotonin itself. This is likely an oversimplification, but my understanding is that SERT modulators include SSRIs (reuptake inhibition), SSREs (reuptake enhancers) or SRAs (agents that work primarily by reversing the transporter through phosphorylation). The action of amphetamine and similar agents is more complicated though, as it also involves VMAT2 inhibition, which prevents monoamines from being packaged in presynaptic vesicles and results in monoamines leaking out into the synaptic cleft though the reversed transporters.
 
I think I read that the tryptamine containing molecule reserpine also acts as a VMAT inhibitor. Immediately after you take it, it was said to cause a surge in monoamines (though I forget which ones), then because all the leaked monoamines get eaten by MAO or COMT then following this surge there is actually depleted monoamines for days afterwards.

I've read some interesting things about reserpine, some authors are even claiming that it is antidepressant.

http://www.ncbi.nlm.nih.gov/pubmed/12953623
 
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