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Pro drugs - Is this even possible?

so many active drugs are prodrugs to other active drugs :meth to amphetamine , Mdma to Mda , Most benzo's to other benzo's.
So yes.

Look up this old thread where me was trying a substance that by any means should have amphetamine in vivo as 1 of the major metabolities , the problem i ran into is that the actual "whole" compound would hit the sigma receptor or any other bodily system that gave me negative effects on several occasions that i did not dared to up my dose to where the amphetamine-metabolite would become active enough to notice:

A first : N-alphamethylbenzyl-amphetamine-bioassay?highlight=ex-amine

I'm sure there must be prodrugs to almost every drug we know , we just have to find out where the binding could be made and what non-toxic part to add to it...and if the whole isn't toxic too !
 
just remembered an old conversation between mr up-and-comming-top-researcher who specialized in peptides , he said that some phenythylamines (or was it tryptamines ? ) could "theoretically" fit in a peptide sequence.
If this could be true , and there would be a way to get them out of the sequence again........
well...just imagine.
 
Any chemical with an amine or carboxylic acid can theoretically fit "in a peptide", doesn't mean that it will enhance activity. The "way to get them out of the sequence" are called peptidase enzymes and they are present in digestive fluids.

Lisdexamphetamine (Vyvanase) is a common example. Even then it was only really developed as a way to avoid abuse - Spansules are a very effective XR mechanism.

Substitution of amino acids (i.e. 5-methoxy-tryptophan, 4-bromo-2,5-dimethoxy-phenylalanine/2cB amino acid) does not produce psychedelic compounds, in general.

Actually, 2-amino-3-(4-bromo-2,5-dimethoxyphenyl)propanoic acid (2c-B amino acid) might be active via aromatic amino acid decarboxylase. I have never looked into it.
 
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sekio said:
Any chemical with an amine or carboxylic acid can theoretically fit "in a peptide", doesn't mean that it will enhance activity. The "way to get them out of the sequence" are called peptidase enzymes and they are present in digestive fluids.

Lisdexamphetamine (Vyvanase) is a common example. Even then it was only really developed as a way to avoid abuse - Spansules are a very effective XR mechanism.
Click to expand...

I can't figure out why people on BL are constantly stating lisdexamfetamine is metabolized into amphetamine by peptidase enzymes in the GI tract. Maybe because there was a thread a while back where someone had claimed they "defeated" the time release by incubation with trypsin?

Peptidase enzymes cleave peptide-peptide bonds. The enzyme binding pockets require a specific peptide sequence for recognition. Amphetamine is not a peptide, and so lysine-amphetamine is not cleaved by peptidase enzymes. All of the studies on the drug's pharmacokinetics have shown that it is non-peptidase enzymes located within red blood cells that convert this prodrug, with absolutely no conversion occurring as a result of pancreatic or hepatic enzymes.

/rant

This was done intentionally - one major issue with other amphetamine XR formulations is that the rate of release is affected by stomach/intestinal contents, and the manufacturer probably needed to avoid this in order to make a substantial claim for novelty (required to patent a drug which is already available off-label).
 
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Neuropharmacological and neurochemical properties of N-(2-cyanoethyl)-2-phenylethylamine, a prodrug of 2-phenylethylamine.


1 N-(2-cyanoethyl)-2-phenylethylamine (CEPEA) was examined as a possible prodrug of 2-phenylethylamine (PEA). 2 Pharmacokinetics of PEA and CEPEA were investigated in rat brain, blood and liver by gas chromatography with electron-capture detection (GC-ECD). Interactions of PEA and CEPEA with putative neurotransmitter amines were investigated by use of high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). 3 Administration of PEA caused transient increases in PEA concentrations which decreased rapidly in brain and blood and at a slower rate in liver. Administration of CEPEA caused sustained elevations of PEA concentrations and elimination of PEA was markedly decreased in these tissues relative to the situation after administration of PEA itself. 4 Administration of CEPEA caused more prolonged decreases in brain noradrenaline, dopamine and 5-hydroxytryptamine concentrations than those observed after PEA administration, although values increased to control levels eventually.
Click to expand...

so maybe prodrugs of PEA, are a way to get PEA active orally without messing with MAOIs? There's more on the side like "N,N-dipropargyl-2-phenylethylamine, a potential prodrug of 2-phenylethylamine: neurochemical and neuropharmacological studies in rat."

Wonder if these would work similarly on amphetamine or meth..
 
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