Why don't non alpha Me phens get quickly metabolized like tryps?

[LucidSDreamr]

Ie why doesn't 2 cb get quickly metabolized ala dmt.

Is it different enzymes that handle tryps and phens or they have greatly variable kinetics on the same enzymes?

 

[Tzcatlipoca]

When you're considering elimination, you need to consider route of administration first. Eaten (oral) dmthuasca can last up to 4 hrs like 2cb, but without a maoi dmt gets monoamine oxylated

 

[LucidSDreamr]

Exactly why doesn't oral 2cb or mescaline require an maoi is what I'm asking

 

[Hodor]

Exactly why doesn't oral 2cb or mescaline require an maoi is what I'm asking

I would assume that the methoxy groups can make a pretty big difference.

Phenylethylamine (as in plain, unsubstituted beta-PEA) is only psychoactive when combined with an MAOI too.

Some enzymes are basically highly selective precision tools. As you said yourself, a single methyl group in the alpha position of a phen or trypt can make a huge difference - whether a substituent on a molecule protects it from being metabolized very much depends on where and how the molecule binds to the enzyme.

 

[Tzcatlipoca]

Consider AMT (alpha-methyl triptamine) orally active without maoi for 6 to 10 hrs

 

[Tzcatlipoca]

I would assume that the methoxy groups can make a pretty big difference.

Phenylethylamine (as in plain, unsubstituted beta-PEA) is only psychoactive when combined with an MAOI too.

Some enzymes are basically highly selective precision tools. As you said yourself, a single methyl group in the alpha position of a phen or trypt can make a huge difference - whether a substituent on a molecule protects it from being metabolized very much depends on where and how the molecule binds to the enzyme.

In pharmachemistry, we call this; when in doubt, cross bind double piperindole rings right in the nitrogen (like they did with Cebranopadol)

 

[LucidSDreamr]

In pharmachemistry, we call this; when in doubt, cross bind double piperindole rings right in the nitrogen (like they did with Cebranopadol)

i'm not getting any google hits on such a search. I don't see what any of this has to do do with the fact that alpha Methylation is rquired on tryps to have oral efficacy, while not in phens

Consider AMT (alpha-methyl triptamine) orally active without maoi for 6 to 10 hrs

yes thats why i posted the question i'm asking in this thread

I would assume that the methoxy groups can make a pretty big difference.

Phenylethylamine (as in plain, unsubstituted beta-PEA) is only psychoactive when combined with an MAOI too.

Some enzymes are basically highly selective precision tools. As you said yourself, a single methyl group in the alpha position of a phen or trypt can make a huge difference - whether a substituent on a molecule protects it from being metabolized very much depends on where and how the molecule binds to the enzyme.

good point about methoxy on the Ph being key...but what about MDMA-without the alpha ME (methylene dioxy phenethylamine for lack of a better name) group?...two nice polar armoatic methoxy type substituents there and no activity.


i'm looking for a mechanistic explaination ideally, scientific papers etc.

anyone know of a non mescaline phen type cnalogue lacking the Methoxy groups and and alpha Me group that still has longer lasting effects? or is it only indole in the aromoatic that seems to be sucemptible to quick degratation in the NON Me cases?

There is 5-meo DMT which lacks aplha Me but has a polar aromatic substituent (Ome) and is quickly degraded anways. But you have things such as psylocybin, psylocin, 4-OAc DMT which have long lasting oral BA so that congradicts the "methoxy/acetoxy on the aromatic theory being required for longevity. But ideally i'd like a more mechanismtic explanation if one exists out there.

its hard to find a pattern...i guess its just how good mao acts on the compound. Wish someone would post a study adressing that very issue accross a very issue. Or even a list of all such drugs and and their durattions and maybe we could see some sort of pattern there.

 

[Tzcatlipoca]

There are DOX, like DOB, DOC, DOI, DOPR, DOET, DOM. Halogenated ones last longest I would say.

 

[Tzcatlipoca]

In fact there was a study that used DOI with the radioactive iodine isotope substituent as radioligand to research dopaminergic / Parkinson's / Alzheimer's related neural deficiency and activity map. Couldn't find on Google, can someone please cite?

 

[clubcard]

In fact there was a study that used DOI with the radioactive iodine isotope substituent as radioligand to research dopaminergic / Parkinson's / Alzheimer's related neural deficiency and activity map. Couldn't find on Google, can someone please cite?

There are dozens of papers that use it for PET. The reason 2CI remained legal in many EU countries when the rest were banned was because of it's utility.

 

[Tzcatlipoca]

There are dozens of papers that use it for PET. The reason 2CI remained legal in many EU countries when the rest were banned was because of it's utility.

Thank you clubcard wonderful point!

 

[LucidSDreamr]

There are DOX, like DOB, DOC, DOI, DOPR, DOET, DOM. Halogenated ones last longest I would say.

these are all alpha methylated like amphetamine is. This is the fact that adds longevity to both phens and tryps I believe. not halogenation. I'm asking why is this alphamethylation the difference between activity and none with tryps, but with phens its not a requirements for the drugs to be orally active

 

[Tzcatlipoca]

In fact there was a study that used DOI with the radioactive iodine isotope substituent as radioligand to research dopaminergic / Parkinson's / Alzheimer's related neural deficiency and activity map. Couldn't find on Google, can someone please cite?

Mate alpha methyl tryptamine (AMT) freebase is orally active and lasts more than 6 hrs?

 

[Solipsis]

Lipophilicity of a compound can make a big difference for ability of enzymes to grapple it, I guess that would be another method than keeping the active site of the enzyme away from liable moieties sterically.

 

[Hodor]

these are all alpha methylated like amphetamine is. This is the fact that adds longevity to both phens and tryps I believe. not halogenation. I'm asking why is this alphamethylation the difference between activity and none with tryps, but with phens its not a requirements for the drugs to be orally active

I think there's a multitude of factors involved. Remember, to elicit a psychotropic effect, the drug needs to get into your brain in the first place (usually by being lipophilic enough to pass through the blood-brain-barrier. Then it has to get past your enzymes - to this end, it needs extra moieties that keep the enzyme from metabolizing it, for example by having groups that get in the way by adding steric bulk. Finally, the drug needs to activate the receptor, which is heavily affected by various moieties through things like steric bulk, the abilitiy to form h-bonds, electronegativity/polarity or the presence of pi-bonds.

With alpha-methylated monoamines, it's probably a combination of better BBB penetration and resistance to monoamine oxidase.

 

[sekio]

The simple answer that nobody has mentioned so far, is that alpha methylated and heavily methoxylated PEAs/tryptamines simply don't fit into the active site of monoamine oxidase any more. Thus, the enzyme can't oxidise them, because the substrate has to fit into the enzyme in order for the reaction to be catalyzed. This results in a sonsiderably longer half life because removal/breakdown of the compounds must occur via other routes like liver metabolism - either oxidatively via CYP enzymes or by having sugars/sulfate groups attached to them via sulfo/gluco-transferase enzymes - or excretion via the kidneys into urine, or partitioning into lipids and excretion in feces.