DOx neurotoxicity

[ohlone]

This 2016 study showed DOI and 5-meo-dipt cause similar neurotoxicity and dna damage as MDMA.
https://link.springer.com/article/10.1007/s12640-016-9654-0
Anyone care to speculate if this neurotoxicity is likely to also occur with the other DOx compounds, related phenethylamines such as the 2C series and mescaline, and other 5-meo tryptamines?

Certainly quite a worrying study.

 

[Hodor]

This 2016 study showed DOI and 5-meo-dipt cause similar neurotoxicity and dna damage as MDMA.
https://link.springer.com/article/10.1007/s12640-016-9654-0
Anyone care to speculate if this neurotoxicity is likely to also occur with the other DOx compounds, related phenethylamines such as the 2C series and mescaline, and other 5-meo tryptamines?

Certainly quite a worrying study.

According to the paper, 2.5 mg/kg of DOI produces a level of DNA damage comparable to 5mg/kg of MDMA...
Seeing as how 5mg/kg of MDMA is a dose you could realistically get from just two of today’s strong extasy tablets, whereas 2.5 mg/kg of DOI would require an adult male to eat at least a whole sheet of DOI blotters, I‘d say there‘s little reason to be concerned about the neurotoxicity of DOx compounds.

 

[Tzcatlipoca]

I ate plenty of dox; dom, dopr, doc, dob, Doi, I feel just fine my friend I am a neuropharmacology undergraduate my colleagues and family can testify to my sanity in case you still doubt it.

 

[clubcard]

I ate plenty of dox; dom, dopr, doc, dob, Doi, I feel just fine my friend I am a neuropharmacology undergraduate my colleagues and family can testify to my sanity in case you still doubt it.

OK - just give me the names, addresses and phone numbers of your colleagues and family and I will get back to you.

 

[Tzcatlipoca]

Yeah I don't like you here. Mods please check this guy?

 

[Zilpe]

To be fair you were relating anecdotal data. How you feel isn't a reliable indicator of whether or not neurotoxicity has occurred and even if it was the experience of a single person in an uncontrolled environment doesn't help.

 

[Cotcha Yankinov]

Yeah I don't like you here. Mods please check this guy?

Fear not, clubcard is a class act

 

[Tzcatlipoca]

Wonderful, thank you Cotcha. Well Dear Clubcard, please feel free to PM me for contact information and I can share my experiences with you. Here I can say I've had DOM tabs dosed at 2.5mg up to 10mgs(4 tabs at once), DOPR tabs dosed at 4mg up to 1,5 tab (6mgs) DOB dosed at 2,5mg up to 5 and, DOI 2,5mg once, DOC up to 8mg with 2mg tabs. None of them lasted shorter than 14hrs. Comeup average 3 hrs, shortest being 2 and longest (DOI) being 4-5 hrs.

 

[clubcard]

Wonderful, thank you Cotcha. Well Dear Clubcard, please feel free to PM me for contact information and I can share my experiences with you. Here I can say I've had DOM tabs dosed at 2.5mg up to 10mgs(4 tabs at once), DOPR tabs dosed at 4mg up to 1,5 tab (6mgs) DOB dosed at 2,5mg up to 5 and, DOI 2,5mg once, DOC up to 8mg with 2mg tabs. None of them lasted shorter than 14hrs. Comeup average 3 hrs, shortest being 2 and longest (DOI) being 4-5 hrs.

Just PM the contact data. You are aware that a sample size of 1 isn't statistically significant? For experiences, we use the term YMMV to underline that fact. If you are keen on the 3-carbon PEA psychedelics with the slow ADME, resolution can be of benefit. If you just draw up the 2,5 IPA in Reaxys as the substructure, it spits out a lot of chiral salts but you will spot the two that were carried out in microscale so if you can obtain sheets, the mechanical losses aren't too bad. It's an interesting corner few have indulged in. I had an idea that (S)DON might make an entactogen. It kind of ½ worked. All I proved was that the (S) isomers caused the unpleasant side-effects in me. Someone else repeating the work would certainly be of benefit to all.

I hope resolution isn't described as synthesis? It's just that the LogP & affinity of the class means that the liver enzymes for o-demethylation have very little opportunity and AFAIK the terminal carbon doesn't get oxidised.

 

[Weltmeister]

If youre on 2.5mg/kg of DOI then neurotoxicity is the least of your worries.

 

[Neithman]

Those rats tripped the biggest balls in history at these dosage,probably started to reevaluate einsteins equivalent

 

[clubcard]

If youre on 2.5mg/kg of DOI then neurotoxicity is the least of your worries.

There are even more potent analogues in the series. A 4-chloromethyl moiety is more potent than the (pseudo)halogens. We know from the 2-carbon class that longer alkyls make stronger compounds but the ADME is soooo slow. I have often pondered the possibility of a prodrug that has a more advantageous pKa. Amino acid amides are cleaved in the blood but I wonder if some amphetamine prodrugs would work in an analogous manner but cleaved within the brain. In a search for less abusable forms of amphetamine, science has resulted in 10 licensed medicines. Adding a ?k is one area of particular interest because pKa is improved a LOT.

I've also noticed that playing with the mesocarb scaffold allows the vital O: of the NBOMe derivatives to be spatially positioned to the same spot (relative to the PEA). If you overlay the NBOMe class and LSD, the -OCH3 overlays the =O, One can only guess what the more rigid PEA derivatives (e.g. TCB-2) would be like.

Interesting stuff but there are so many known but untested toxic activity in all of these classes. The NBOMes especially. I'm interested in these classes but I'm still not comfortable that they are replacing LSD. Real lysergic acid amides with various 8 substitutions gives a decent palette. Most of all I love DMT which is why I was so pleased to discover that 7 methyl DMT is, if anything better than the parent compound. It brings forth more euphoria but have you taken a look at the indole synthesis? Cannot see that one appearing anywhere anytime soon.

 

[Hodor]

I've also noticed that playing with the mesocarb scaffold allows the vital O: of the NBOMe derivatives to be spatially positioned to the same spot (relative to the PEA). If you overlay the NBOMe class and LSD, the -OCH3 overlays the =O, One can only guess what the more rigid PEA derivatives (e.g. TCB-2) would be like.

You mean a TCB-2 NBOMe? They already made that... supposedly not much more active than plain TCB-2 though, IIRC. Or a TCB-mesocarb-NBOMe? Not sure if that weird sydnone imine thing is a bioisotere for a simple secondary amine as far as receptor binding is considered. Otherwise getting that O in just the right position probably isn't going to help much.

You ever heard of Juncosamine ("DMBMPP"), btw? By spanning a rigid piperidine ring between the alpha-carbon and the benzyl, they were able to attain an extremely high level of selectivity for 5HT2A over 5HT2C with the S,S-isomer.

Interesting stuff but there are so many known but untested toxic activity in all of these classes. The NBOMes especially. I'm interested in these classes but I'm still not comfortable that they are replacing LSD. Real lysergic acid amides with various 8 substitutions gives a decent palette.

I think the NBOMe craze has mostly died down now that they're illegal pretty much world-wide. Sure, you still regularly find NBOMe blotters on the street, but only a fraction of what it was a few years ago. The darknet has probably made real LSD more affordable than it has been in decades, and clearnet lysergamide vendors have been making other lysergamides available to the general public for basically the first time in history. It's really a crying shame that - given the high complexity/low yield of the synth - we're probably not going to see any significant amount of the 6-substituted lysergamides being synthed in the future, now that many European nations (which were probably the main market for these) have enacted blanket bans on NPS compounds

 

[Tzcatlipoca]

You mean a TCB-2 NBOMe? They already made that... supposedly not much more active than plain TCB-2 though, IIRC. Or a TCB-mesocarb-NBOMe? Not sure if that weird sydnone imine thing is a bioisotere for a simple secondary amine as far as receptor binding is considered. Otherwise getting that O in just the right position probably isn't going to help much.

You ever heard of Juncosamine ("DMBMPP"), btw? By spanning a rigid piperidine ring between the alpha-carbon and the benzyl, they were able to attain an extremely high level of selectivity for 5HT2A over 5HT2C with the S,S-isomer.



I think the NBOMe craze has mostly died down now that they're illegal pretty much world-wide. Sure, you still regularly find NBOMe blotters on the street, but only a fraction of what it was a few years ago. The darknet has probably made real LSD more affordable than it has been in decades, and clearnet lysergamide vendors have been making other lysergamides available to the general public for basically the first time in history. It's really a crying shame that - given the high complexity/low yield of the synth - we're probably not going to see any significant amount of the 6-substituted lysergamides being synthed in the future, now that many European nations (which were probably the main market for these) have enacted blanket bans on NPS compounds

Wow, Today I Learned. Thank you guys. One lysergamide that was very interesting to me that I never got to try is Lysergic Acid Morpholide(LSM) available from a clearnet vendor supposedly 1/10th potency of LSD with activity at Mu and Delta...

Best,
Tez

 

[clubcard]

You mean a TCB-2 NBOMe? They already made that... supposedly not much more active than plain TCB-2 though, IIRC. Or a TCB-mesocarb-NBOMe? Not sure if that weird sydnone imine thing is a bioisotere for a simple secondary amine as far as receptor binding is considered. Otherwise getting that O in just the right position probably isn't going to help much.

You ever heard of Juncosamine ("DMBMPP"), btw? By spanning a rigid piperidine ring between the alpha-carbon and the benzyl, they were able to attain an extremely high level of selectivity for 5HT2A over 5HT2C with the S,S-isomer.



I think the NBOMe craze has mostly died down now that they're illegal pretty much world-wide. Sure, you still regularly find NBOMe blotters on the street, but only a fraction of what it was a few years ago. The darknet has probably made real LSD more affordable than it has been in decades, and clearnet lysergamide vendors have been making other lysergamides available to the general public for basically the first time in history. It's really a crying shame that - given the high complexity/low yield of the synth - we're probably not going to see any significant amount of the 6-substituted lysergamides being synthed in the future, now that many European nations (which were probably the main market for these) have enacted blanket bans on NPS compounds

No, just plain TCB-2.

 

[Tzcatlipoca]

There are even more potent analogues in the series. A 4-chloromethyl moiety is more potent than the (pseudo)halogens. We know from the 2-carbon class that longer alkyls make stronger compounds but the ADME is soooo slow. I have often pondered the possibility of a prodrug that has a more advantageous pKa. Amino acid amides are cleaved in the blood but I wonder if some amphetamine prodrugs would work in an analogous manner but cleaved within the brain. In a search for less abusable forms of amphetamine, science has resulted in 10 licensed medicines. Adding a ?k is one area of particular interest because pKa is improved a LOT.

I've also noticed that playing with the mesocarb scaffold allows the vital O: of the NBOMe derivatives to be spatially positioned to the same spot (relative to the PEA). If you overlay the NBOMe class and LSD, the -OCH3 overlays the =O, One can only guess what the more rigid PEA derivatives (e.g. TCB-2) would be like.

Interesting stuff but there are so many known but untested toxic activity in all of these classes. The NBOMes especially. I'm interested in these classes but I'm still not comfortable that they are replacing LSD. Real lysergic acid amides with various 8 substitutions gives a decent palette. Most of all I love DMT which is why I was so pleased to discover that 7 methyl DMT is, if anything better than the parent compound. It brings forth more euphoria but have you taken a look at the indole synthesis? Cannot see that one appearing anywhere anytime soon.

I have heard of a sea sponge that produces 5-bromo-dmt and that the oral experience is quite pleasant, much like the 5-meo-mipt/dipt (foxy/moxy) you would perhaps be interested in, clubcard?
Source: https://www.reddit.com/r/Drugs/comments/3pwjuw/5bromodmt_aka_5brdmt/
Your brother,
Tez

 

[Weltmeister]

You mean a TCB-2 NBOMe? They already made that... supposedly not much more active than plain TCB-2 though, IIRC. Or a TCB-mesocarb-NBOMe? Not sure if that weird sydnone imine thing is a bioisotere for a simple secondary amine as far as receptor binding is considered. Otherwise getting that O in just the right position probably isn't going to help much.

You ever heard of Juncosamine ("DMBMPP"), btw? By spanning a rigid piperidine ring between the alpha-carbon and the benzyl, they were able to attain an extremely high level of selectivity for 5HT2A over 5HT2C with the S,S-isomer.



I think the NBOMe craze has mostly died down now that they're illegal pretty much world-wide. Sure, you still regularly find NBOMe blotters on the street, but only a fraction of what it was a few years ago. The darknet has probably made real LSD more affordable than it has been in decades, and clearnet lysergamide vendors have been making other lysergamides available to the general public for basically the first time in history. It's really a crying shame that - given the high complexity/low yield of the synth - we're probably not going to see any significant amount of the 6-substituted lysergamides being synthed in the future, now that many European nations (which were probably the main market for these) have enacted blanket bans on NPS compounds

In most european countries theyre still legal actually. In the biggest market in europe germany theres only a ban on phenethylamines and cannabinoids with similar structure to jwh-18.

 

[5ht2Antogonist]

So.. are NBOMe's relatively more toxic than DOx compounds? If yes, what is the real reason behind this?

Are both these substance groups have a LD50 ?

(I just assumed that we could apply the DOI toxicity report to NBOMe's as well.. that's why I m curious )

 

[Cotcha Yankinov]

One of the main concerns with NBOMEs is that in overdose they can lead to fatal vasoconstriction of the arteries that supply the brain.

While ergotamine has been used for ages to constrict arteries in situations where that is desirable, deaths due to NBOME overdose IIRC are typically due to cerebral vasoconstriction. I imagine that there are situations where the vasoconstriction can also add to deleterious effects of NBOMEs, death notwithstanding.

One of the reasons for this is that NBOMEs tend to be much more full agonists at e.g. 5-HT2A than many other hallucinogenic 5-HT2A ligands, so while classical hallucinogens do produce vasoconstriction via actions at e.g. 5-HT2A receptors, its much more potent with NBOMEs.

 

[clubcard]

I have heard of a sea sponge that produces 5-bromo-dmt and that the oral experience is quite pleasant, much like the 5-meo-mipt/dipt (foxy/moxy) you would perhaps be interested in, clubcard?
Source: https://www.reddit.com/r/Drugs/comments/3pwjuw/5bromodmt_aka_5brdmt/
Your brother,
Tez

The only tryptamines that interest me are the 7-methyl derivatives. They are all potent serotonin releasing agents. 7,n,n-TMT is better than DMT (IMHO) but as I said, look how much fun making the indole is! The AMT & AET become simply HUGE serotonin-releasers. Careful, they are MAOIs. I found that the chiral resolution of those last to is of immense benefit. Only the (S) is a 5HT-2a ligand i.e. the (R) isomers are entactogens. Very nice ones but as I said, MAOIs so the project was buried (but look on Reaxys). I had much more luck with the aminorex class. Not the 4-methyl derivatives. Dr. Dave has all my paperwork and pointed out that 'Serotonia' AKA p,4-dimethylaminorex is an MAOI (hence some deaths) while aminorex isn't. A 2:1 ratio of p-Me & m-Me is like MDMA on steroids. There is ALWAYS a problem though, isn't there? The ring-closure requires a compound that is a)as toxic as hydrogen cyanide OR another extremely expensive an unstable cyanamide (see Reaxys).

Last thought, people who like pyrovalerone analogs should check out 1-(4-methylphenyl)2-phenyl-3-(pyrrolidin-1-yl)ethanone. The cLogP is much higher so it accumulates in fatty tissue (like the brain) as opposed to watery tissue (like peripheral nervous system). It was wasted on me, it was as horrible as cocaine. On the other hand, my wife loved it BECAUSE it was like cocaine. That p-Me is important; it increases selectivity to dopanine AND provides the body with a sacrificial site for the body to oxidize.

I do hope I haven't overstepped the mark. I didn't sit down and micro-scale them all; a team spat out large numbers of related compounds to establish QSAR. I can only presume that the rats died happy. Anyone who is familiar with this knows the RRR axiom. First caring for rodents, then sacrificing them, microtoming, mounting and staining brain tissue does tarnish the soul... no, a couple of decades ago when the weight of the world hadn't crushed my soul ;-)