Tuesday, December 22, 2009


Fun with trace amines and enzyme inhibition

I went to whole foods today and asked if they sold phenethylamine or PEA, they led me to their phenylalanine.
"No not phenylalanine - Phen-Ethyl-Amine"
"What's it do?"
"It's a stimulant"
"Oh no stimulant is not a Whole Foods word, cummon man, stimulant is not a Whole Foods word!"

PEA is a trace amine, putative neurotransmitter, and the chemical backbone of most dopaminergic stimulants. Additionally it's reported to be more addictive than amphetamine (of which PEA is the parent compound). It's unclear to me if this is because it's a qualitatively superior stimulant (likely) or because the shortened duration makes it fit the classic criteria for an addictive drug ((fast onset/short duration/frequent administration required) also likely) the reason that PEA has not gained widespread popularity is that it's almost immediately deaminated by MAO rendering it inactive moments after ingestion. There are two popular ways of overcoming the enzymatic tyranny of MAO, the first being direct inhibition via a pharmaceutical MAOI (with the MAO-B selective selegiline being most popular) and the second is to overwhelm MAO by taking megadoses in excess of a gram. With MAO-B inhibition the dose of PEA is comparable to amphetamine i.e., 25mg is reported to be very strong.

It seems to be a small minority of people that can play with the selegiline+PEA combo without getting miserably addicted, perhaps even a minuscule minority. In many ways it's the holy grail of stimulants: (arguably) safe, dirt cheep, and completely legal. Yet it's not something people can use responsibly. So how can one change this, how can one take advantage of this beautiful molecule which holds so much potential? PEA has a half life of 1 minute ((comp. to smoked crack which has a half life of 56 min) although PEA's t1/2 must be longer with MAO inhibition (more research is required)) thusly it necessitates continuous redosing - the first solution is to create some kind of mechanical time release mechanism, I'll leave that to others. the second is to introduce a time release mechanism into the molecule itself รก la vyvanse.

So here is my solution: lys-PEA aka alpha-desmethyl-lisdexamfetamine. a time release PEA prodrug, when taken with a MAOI it should have a long and healthy duration (I'm guessing something closer to normal dexamp sans lysine) a low dose, low toxicity, and ultra-low illegality. It will overcome the SAS criterion I outlined above and will probably be an incredibly effective ADHD treatment. The TRUE holy grail of psychostimulants. perhaps it would even be embraced by whole foods, after all lysine and phenethylamine are both TOTALLY natural. I only want to help people.

Equilibrium dissociation constants:

Phenethylamine: NE: 10.9; DA: 39.5; SE > 10000.*
Amphetamine: NE: 7.07; DA: 24.8; SE: 1765.
Methamphetamine: NE: 12.3; DA: 24.5; SE: 736.

*gotta love the way it gives 5HT the cold shoulder, harsh bro!