Acetylcholinesterase inhibitors

[MrHH]

I was curiously thinking yesterday night about what can happen if an Acetylcholinesterase inhibitor is mixed as a preload of an Acetoxy compound.

Does it allow to experience a trip more similar to what pure 4-AcO-* substances might feel if they would not become naturally 4-HO-* in vivo? In other words: Is there any safe way to avoid the in-vivo hydroloxys of 4-AcO substances in 4-HO?

If possible, this would allow to purely experience the 4-AcO compounds (without any 4-HO effect), which are also supposed to enter the Blood-Brain barrier by themselves.

 

[adder]

What makes you think 4-AcO-DMT might be metabolised to 4-HO-DMT by AChE? I seriously doubt that 4-AcO-DMT would fit into AChE to be metabolised.

The way heroin is rapidly metabolised to 6-acetylmorphine is through hydrolysis, so this is simply done with water without any specialised enzymes involved, that's why it happens so fast. In the same way a simple ester like for instance ethyl propionate would react with water to give propionic acid and ethanol, no catalysts are necessarily involved here. I doubt that you can inhibit the metabolism of 4-AcO-DMT because your body is mostly water, so once you ingest it, there is no way it wouldn't be hydrolysed.

Anyway, is there any proof that all psychoactive effects of 4-AcO-DMT come from 4-HO-DMT? I doubt that there were any studies done on it, however, it is very likely 4-AcO-DMT is hydrolysed to 4-HO-DMT.

 

[MrHH]

What makes you think 4-AcO-DMT might be metabolised to 4-HO-DMT by AChE? I seriously doubt that 4-AcO-DMT would fit into AChE to be metabolised.

The way heroin is rapidly metabolised to 6-acetylmorphine is through hydrolysis, so this is simply done with water without any specialised enzymes involved, that's why it happens so fast. In the same way a simple ester like for instance ethyl propionate would react with water to give propionic acid and ethanol, no catalysts are necessarily involved here. I doubt that you can inhibit the metabolism of 4-AcO-DMT because your body is mostly water, so once you ingest it, there is no way it wouldn't be hydrolysed.

Ok... About being hydrolysed with existing water in our organism, it has completely the entire sense. I was just trying to figure out a possible way to do that (avoid the hydrolosys as much as possible), and the AChE inhibitor 'looked' to apparently have relationship with that. It would be extremely interesting to find a way to do that since we will be able to demonstrate that Acetoxy compounds are active by themselves, and to try to experiment a -more- 'raw' acetoxy experience. Nevertheless, thinking about the fact that hydroloxys is also triggered by the fluids on the body, it makes it very difficult I think.

Anyway, it is interesting enough to ask why small amounts of the original acetoxy molecule remains untouched, therefore, affecting to the overall experience; since strictly following "the established theory" would result in the fluids & acids on stomach quickly degrading ENTIRELY the substance, no? Maybe the needed amount of fluids/water is not enough? Can eating/preloading/combining with other substances or aliments make a difference on this?

Anyway, is there any proof that all psychoactive effects of 4-AcO-DMT come from 4-HO-DMT? I doubt that there were any studies done on it, however, it is very likely 4-AcO-DMT is hydrolysed to 4-HO-DMT.

I think there were some references on the first pharmacology book from Shulgin (or TiKHaL, I do not remember exactly), but I am not sure if it was a purely suggestion or a demonstrated fact.

 

[Solipsis]

Even if acetylcholinesterase weren't selective for acetylcholine (which it probably is though), I doubt inhibiting would do much good since there are likely a lot more esterases in the body that can still do the job of deacetylating 4-AcO trypts.

 

[Goddess Mode]

MrHH, I've actually been wondering this myself. I have a good number of test compounds to work with on both sides, so I'll probably get around to it eventually....

What has been said so far is inaccurate.... Heroin does indeed get metabolized by acetylcholinesterase. Both that and butyrylcholinesterase in red blood cells are responsible for converting heroin into 6-monoacetylmorphine, and then only acetylcholinesterase is responsible for further converting that into morphine itself. Interestingly, brain acetylcholinesterase is incapable of hydrolizing heroin. This is all detailed here.

In addition, it has been showed that 5-acetoxytryptamine is hydrolized by both acetylcholinesterase and butyrylcholinesterase, shown here. With that in mind, it actually seems not only possible to me but in fact fairly likely that 4-acetoxy tryptamines are cleaved in this way as well. However, the real question is whether or not it would really make any difference to inhibit this process... because as Solipsis said, just because you stop one esterase mechanism doesn't mean that others won't pick up the slack.

Anyway, if you do give it a try at least take some precautions and make sure you get something that inhibits both acetylcholinesterase and butyrylcholinesterase. I'll be doing the same some day.

 

[MrHH]

I am very happy to hear that I were not so lost

Maybe other ROA is the answer to prevent the hydroloxys caused by the fluids in first instances before the metabolization? If we could get a way to prevent the exposure to water/liquids... that would be a step.

I think it's a pretty interesting experiment. It would be extremely helpful if someone knowledgeable can confirm that inhibition of AChE before/during consumption of a 4-AcO tryptamine is not going to have a negative/unpredictable effects as a result. I love to be an explorer/researcher but I try take care for myself

 

[adder]

Maybe other ROA is the answer to prevent the hydroloxys caused by the fluids in first instances before the metabolization? If we could get a way to prevent the exposure to water/liquids... that would be a step.

How do you plan to prevent exposure to blood? Without fluids no transport inside the body would actually be possible.

 

[Goddess Mode]

Haha, yeah you're probably going to have a pretty difficult time stopping it completely. I guess I think of it this way.... If other esterases in the body can pick up the workload for acetylcholinesterase, then I wouldn't be too surprised if the same is true for acetylcholine itself. Despite this, acetylcholinesterase inhibitors do significantly increase levels of acetylcholine, even if they don't also inhibit butyrylcholinesterase. It would make sense that even if other enzymes can do this same job, inhibiting the main one that does iit would still increase levels of the compound. If these enzymes are also the same ones that deactylate the tryptamines, then the same relationship would probably exist, so you wouldn't necessarily need to do anything more than that for at least *some* potentiation. Just how potent do you need it to be?

 

[Hecticus]

Would the acetoxy compounds hydrolyse upon entering the blood stream through intravenous use? I assume so if i read correctly.

But i've also read other reports coming to the conclusion that acetoxy must active since they are very effective when used intravenously?

 

[sekio]

But i've also read other reports coming to the conclusion that acetoxy must active since they are very effective when used intravenously?

So is heroin, though, and it's established that most of the activity resides in its hydrolysis products.