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Esters of Phenylalanine

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c0rt3x

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I've just synthesised phenylalanine ethyl ester in order to research this compound. I've consumed about 50mg of it until now and it seems to have some enjoyable stimulating effect!

But I'm not sure wheter or not this was just a placebo effect since I took 2x20mg D-Amphetamine several hours ago - but I don't think so. I'm going to take another dose soon and then I will report again.


However I'm going to synthesize other esters of Phenylalanine tomorrow.


Untill then please tell me your theories about phenylalanine ethyl ester's pharmacology and metabolism.

Thanks.
 
Well that would get something roughly analogous to Ethylphenidate whereas ritalinic acid is inactive.

If only it were that easy ;)
 
c0rt3x said:
I've just synthesised phenylalanine ethyl ester in order to research this compound. I've consumed about 50mg of it until now and it seems to have some enjoyable stimulating effect!

But I'm not sure wheter or not this was just a placebo effect since I took 2x20mg D-Amphetamine several hours ago - but I don't think so. I'm going to take another dose soon and then I will report again.


However I'm going to synthesize other esters of Phenylalanine tomorrow.


Untill then please tell me your theories about phenylalanine ethyl ester's pharmacology and metabolism.

Thanks.
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Is it the hydrochloride or free base? The free base will not be very stable, but will form slowly a cyclic dipeptide. Phenylalanine ethyl ester is a substrate for hydrolysis by chymotrypsin, a digestive enzyme in the stomach, so I doubt that it survives long enough after oral ingestion to get much of it into the bloodstream.
 
Is it the hydrochloride or free base? The free base will not be very stable, but will form slowly a cyclic dipeptide. Phenylalanine ethyl ester is a substrate for hydrolysis by chymotrypsin, a digestive enzyme in the stomach, so I doubt that it survives long enough after oral ingestion to get much of it into the bloodstream.
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It was the sulfate.

Since I sniffed it instead of consuming it orally this should'nt play any role...
 
Here is a little tip for you:

Don't take powerful drugs (Amphetamine) on the same day you try to bioassay a completely unknown substance.
 
Actually the one that is analogous with ethylphenidate possesses the ester on the beta carbon.

The citations in the other thread were referring to this compound.

Esterifying phenylalanine sounds like too good to be true basically.

I was having a discussion with Murphy about reactions on phenylalanine to make 3-benzylmorpholine.

what you are proposing is practically laughable.
 
Here is a little tip for you:

Don't take powerful drugs (Amphetamine) on the same day you try to bioassay a completely unknown substance.
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Yeah - of couse you're right. But on the other site: I'm quite convinced that I had not even thought about those esters if I had not been on D-Amphetamine because I've got pronounced strong A.D.D ...


At least the DL-Phenylalanine Glycerol ester is definitely active since it caused some obvious visual changes - at a sigle dose of ~10 mg - wich are extremly unlikely to be only placebo effects. However this compound caused me to sweat and did'nt felt really enjoyable. But at least this shows that researching other esters of DL-Phe are worth a try :-)
 
Do you know anything about zylofuramine?

Now that could be an interesting one.

Clearly the esters idea is a possibility. If anybody discovers something that would be a treat.

I wonder what the chances are?
 
Although it was all already said, I may summarize it once again:

1. Any bioassay on a formerly untested compound is meaningless if you have taken 40 mg amphetamine before. Furthermore, the expecting attitude of such an experiment excludes any direct derivation of conclusions, in particular if 'the felt effects' were only very weak ones. Self-imagination anyone? *yawn*

2. Phenylalanine ethyl ester gets most probably metabolized very fast and very effectively. The t1/2 of the corresponding methyl ester in human blood is around 3-4 minutes, in plasma ca. 20-30 min. See e.g. Journal of Nutrition 1984, 114, p.1940, if I may quote:
Comparison of the areas under the PM and total 14C-blood concentration-time curves indicated that only 0.2% of the administered PM reached the portal blood unchanged, and 0.1% or less reached the peripheral blood unchanged. Blood and plasma from monkeys and humans hydrolyzed PM in vitro at very similar rates, but plasma PMase activity was much higher in the dog and rat than in the monkey or human.
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So 0.1% or less? Wow. You see me astonished...........not! :\ You have taken 50 mg, which will get metabolized almost quantitatively before it even reaches the outer frontiers of your tangled brain.

What else do you need? This whole proposal lacks any viable background to be based on and is IMHO more hoping than knowing anything feasible. Period.

- Murphy
 
Although the fact that the methyl ester gets metabolised very quickly indicates that the same would occur for the ethyl ester, this is not definitively the case.

The OP is going to try it again whilst not under the influence of d-amphetamine, and this will provide a much clearer picture. No need to dismiss it so instantly, just to display your god-like knowledge of all pharmacology. Give the guy a chance. I have no need to insult you and I doubt that the OP ever has either. So to refer to my brain as 'tangled' and to constantly write *yawn* is completely unnecessary.
 
What is your prove for this statement? Significant differences in the speed of metabolism between the methyl resp. ethyl ester are unlikely, to put it mildly.
 
esters hydrolyse at a rate that is dependant on whether there are electron donating or withdrawing substituents on the alfa carboxylic position or on the alcohol.

there is bugger all difference between methyl and ethyl phenylalanine in this respect.
 
Anyhow, your knowledge about basic biochemistry seems to be non-existent so far. :\ Quite a futile discussion, I have to admit.

Carboxylesterases are known for their really broad (!) substrate spectrum, one methylene group being a negligible difference, in particular if the structural difference is in the alcohol part of the ester rather that in the acid part.

As you seem to believe solely to peer-review data, you may like to have a look at Journal of Pharmacology and Experimental Therapeutics 2006, 316, p.572. There are some kinetic parameters for just one isoform of porcine liver microsomal carboxylesterase given (for the hydrolysis of phenylalanine ethyl ester), for example the vmax-value: 11859.78nmol/min/µg. That is already incredibly fast.
Now consider that there is for sure not just one liver carboxylesterase but several isoforms.
Consider also that carboxylesterases are very common in other tissues as well, including the intestinal tract, the blood.

There's no need to elaborate any further.


In short: This whole proposal says that phenylalanine is psychoactive, which is NOT true.

- Murphy
 
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