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least # of ring substituents on PEA to bypass MAO degradation?

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gladiolus

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Hi, I'm not necessarily talking about hallucinogens...but obviously the typical 2,4,5 pattern prevents MAO breakdown of the PEA molecule. But can we simplify it even further? How about just a 4 substituent? For example, given that 4-meo has MAOI properties, maybe 4-meo PEA would get thru first oral bypass withut being degraded by MAO. What about the 4-F or 4-methyl?
Or any thoughts about simple subs at just the 5 and the 2 position?
Has anyone tried 4-meo PEA, or MDPEA - any info out there?
 
Methamphetamine is pretty resistant to MAO breakdown, and that has no ring substitutions. The n-Methyl group protects it from n-oxidation.
 
Pretty sure one needs at least a substitution at 2 spots on the ring beofre a plain PEA becomes active.
See MAPEA and MEPEA, 3-methoxy-4-allyloxy (or ethoxy) PEA - pretty much the 'simplest' pea's still active orally.
 
Does anyone know if 4-methoxy-PEA is active? Or better, 4-methylthio-PEA?
 
Hmmm interesting. The 4-F substituents are the safest and least toxic halides to put on the ring. If the 4meo works then I'm pretty darn sure the F would work, not 100% sure tho.
The reason I ask is that I love the pure rush of plain PEA compared to the 'phetamines, and to not have to take it with an MAOI-B by a simple 4-addition would presumably not alter the chemical landscape of the drug - much - or as much - as alphamethylation.
Also, F addition at the para position is pretty easy to make from plain PEA.

EDIT
see here:

http://www.ncbi.nlm.nih.gov/pubmed/6447879

for confirmed activity of 4F-PEA. It seems the meo, Cl, Br, I all induce serotonin syndrome readily in the mouse. 4-F substitution makes a molecule with primarily serotonin agonist properties however - might even be hallucinogenic. Seems like 4FPEA might be the safest of all of these.

Did shulgin get it wrong then when he claimed MD-PEA was inactive?

This article seems to suggest that 3-meo PEA is orally active too, bypassing MAO:

http://pubs.acs.org/doi/abs/10.1021/bi0110037

Above article suggests both 4meo and 3meo PEA break down into dopamine.

Man, 4FPEA so easy to get too. Who's going first?
 
Last edited:
gladiolus said:
Hi, I'm not necessarily talking about hallucinogens...but obviously the typical 2,4,5 pattern prevents MAO breakdown of the PEA molecule. But can we simplify it even further? How about just a 4 substituent? For example, given that 4-meo has MAOI properties, maybe 4-meo PEA would get thru first oral bypass withut being degraded by MAO. What about the 4-F or 4-methyl?
Or any thoughts about simple subs at just the 5 and the 2 position?
Has anyone tried 4-meo PEA, or MDPEA - any info out there?
Click to expand...

Back to the original question, which was MAO substrate activity, not bioactivity. Here is a list of MAO substrates from an old paper: CLARK LC, BENINGTON F, MORIN RD.
“THE EFFECTS OF RING-METHYOXYL GROUPS ON BIOLOGICAL DEAMINATION OF PHENETHYLAMINES”.
J Med Chem. 1965 May 01;8:353-5.


Note that all monomethoxyphenethylamines are substrates, and of the dimethoxy analogues, only 2,6-dimethoxy is not a substrate. Any trimethoxyphenethylamine with 2,6 substitution is not a substrate. 2,4,5-Trimethoxy is a weak substrate. Interestingly, 3,4,5-trimethoxy (mescaline) is only a substrate for the semicarbazide sensitive amine oxidase (SSAO), not monoamine oxidase (MAO), as can be seen by comparing the columns with and without semicarbazide. The tetra and pentamethoxyphenethylamines are not substrates for either enzyme. Of course, the compounds which are not substrates could be inhibitors.
 
beta-Phenylethylamine is active on it's own, providing euphoria, stimulation, sociability, etc. Alexander Shulgin was wrong! I know from experience. Different feel from amphetamine, by the way. Feels WAY more 'lovey-dovey' and sociable.
 
Right, your placebo affect vs. the 95% of the world who'll say you're wrong?

Talk to people who've actually knocked out MAO-B and tried it.
 
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