Phenethylamines Self experiments with new series of NXXX-phenylethylamines

[Erikmen]

No problem, just a friendly warning, and indeed an early warning - it is very vague grey area stuff what counts and what doesn't, sometimes.

In NSP there is a thread for talk about semi random structural formulae people like to draw. Encouragement of actual drug development like we touch on in this thread can be iffy: we are simply not here to help others acquire or make drugs. While I think that Hans has got it covered without us, and his reports on what he has chosen to do are interesting for us to read, I just need us to be careful about getting too interactive.

Because it is really interesting!

 

[Rokk]

No problem, just a friendly warning, and indeed an early warning - it is very vague grey area stuff what counts and what doesn't, sometimes.

I have to agree with that. After browsing around for a while, so far my take on what is allowed and what is not is "It depends...."

My reasons for finding out and publishing new research chemicals
Humans need an intoxication or drunkenness or ecstasy from time to time. And they should be allowed to decide by their owne, wich one and with wich means. Not the drug produces dependence or addiction, on´s character structure leads to excessive use, suggesting problem-solving of distressing feelings. Dependence should be seen as it is: not produced by a drug, but rather as a psycho-social problem.
War on drugs will continue. Eugene Jarecki carfully researches show the political reasons for this war and failure for a policy that is urgently in need of rethinking, followed by discrimination of and war on the BLACK
(Eugene Jarecki and the campaign to end America's war on drugs: http://www.theguardian.com/society/2...i-war-on-drugs).
A big industry of suppression and repression has taken on a life of its own and can hardly be stopped. Discrimination and Illegalisation of most of the outlawed hallucinogens (e.g.Mescaline, MDMA, LSD, Psylocybin...) leads scandalously to discrimination and illegalisation of a very helpfull psychotherapy: the psycholytic therapy. However, I hope the wave of research chemicals will help to build up more pressure in discussing and legislating for more liberalisation and more intelligent use of drugs.

Thank you for this enlightened post. Younhave got it so right Hans. I share your sentiments exactly. Children spin in circles because it is the nature of the human spirit to expand and explore the limits of our conciousness. Nothing the authourities do will alter this fact. It will never change Law enforcement repression has caused more harm to the community than any other single thing I can think of. Their efforts result in the repression of the free flow of information that could and would save many from harm, without question.

 

[Hans Meyer]

reply to Rokk

I have to agree with that. After browsing around for a while, so far my take on what is allowed and what is not is "It depends...."



Thank you for this enlightened post. Younhave got it so right Hans. I share your sentiments exactly. Children spin in circles because it is the nature of the human spirit to expand and explore the limits of our conciousness. Nothing the authourities do will alter this fact. It will never change Law enforcement repression has caused more harm to the community than any other single thing I can think of. Their efforts result in the repression of the free flow of information that could and would save many from harm, without question.

I am really happy, that someone agrees with my thoughts on the use of drugs! Thanks a lot! I am pressed in time for now, therefor later more. LG Hans

 

[Hans Meyer]

Table of SV (update: Table of SV_v2.2.1)

"Self-testing of new Phenyethylamin substances of the NXXX-phenyehthylamin class". Here comes an update of the "Table of SV": Table of SV_v2.2.1. Hans M.

 

[Hans Meyer]

2C-C-N2Nap1Br or 25C-N2Nap1Br

*********************************************
2C-C-N2Nap1Br or 25C-N2Nap1Br* date 151025
*********************************************
*nomenclature follows the rules of Michael R. Braden et al: Molecular interactions of serotonin 5-HT2A receptor residues Phe339 and Phe340 with super-potent N-benzyl phenethylamine agonists. Department of Medicinal Chemistry and Molecular Pharmacology School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907;

IUPAC-Name:
N-[(1-bromo-2-naphthyl)methyl]-2-(4-chloro-2,5-dimethoxy-phenyl)ethanamine

Structure:

Trial 1:
Salt: Sulfate
Dose of free base [nMol/kg]; (M=434.7 g/Mol): 1.459 nMol/kg
Dose [µg] of free base related to a 75 kg body: 48 µg
Route of Administration: s.l. (sub lingual)
Duration: ~ 4 h
Notes: 8.June 2015; 14:00h ~60µg sulfate in ~15µL etOH s.l.; ~16:00h smooth weak effect, beeing dull a littl bit, something not on a comfy couch. 17:30h seems to be finished, a touch of beeing narcotic. 23:00h had a nice evening. 23:30h to bed, incredible pictures during falling asleep. Above threshold.

Trial 3:
Salt: Sulfate
Dose of free base [nMol/kg]; (M=434.7 g/Mol): 4.377 nMol/kg
Dose [µg] of free base related to a 75 kg body: 143 µg
Route of Administration: s.l.
Duration: ~ 6 h
Notes: 9.July 2015; 17:30h ~180µg s.l., then nordic walking 2h; very nice walking, clear thoughts. 21:00h turned on, but hardly (+); nice relaxed evening. 23:00h to bed, good sleep, but was aware of going on at a low level all the night, so sleep was a little bit not as deep as usual.

Trial 4:
Salt: Sulfate
Dose of free base [nMol/kg]; (M=434.7 g/Mol): 9.727 nMol/kg
Dose [µg] of free base related to a 75 kg body: 317 µg
Route of Administration: s.l.
Duration: ~ 10(?) h
Notes: 5.Sept.2015; 8:30h ~400µg sulfate s.l.; 9:00h it works! 9:30h nordic walking quite nice, but deeper emotions (normal experience of nature) failed, despite more clear sight; all a little bit subdued mood. 12:00h seems coming down; 13:00h comes again in waves; guitar-music, very impressive, analytical insights: concerning the very early years of my childhood. 15:30h into the garden, very impressive nature, clouds, sun, wind, flowers. On the whole: subdued mood (but that may be owed to the Trimipramin (an Antidepressive) that I take (low dose 7mg/d) against my depressions since some weeks.). (+) and sometimes (++) (on couch with music). Nice afterglow. 24:00h: still not be sleepy. Later on, sleep was a liitle bit not as deep as usual.

More details can be seen here (Russian Hyperlab, they accept English too):
https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=31263
(and click "continue" further down)

Own comments need registration i.e. under
https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=30352&lang=en

The links are SURE! despite warnings.

 

[Bagseed]

Trimipramin is a 5HT2-A antagonist, so that might considerably inhibit the psychedelia of your compound. anyway, nice report, and your 400µg trial sounds pretty interesting.

 

[Hans Meyer]

Trimipramin is a 5HT2-A antagonist, so that might considerably inhibit the psychedelia of your compound.

So I think too, therefore I mentioned it. But this could mean that the subdued mood owes as a side effect of the trimipramine, and 2CC-N2Nap1Br could work even at the sub-400µg-level.

 

[Bagseed]

what would be really interesting is some receptor affinities for your compounds, but I guess this will be difficult to achieve. :/

accomplishing the synthesis of an N-Benzyl-Phenethylamine active in sub-mg doses but without the full agonism (which is the probable reason of the toxicity of the classic NBOMe compounds at least as far as I know) would be quite something!

how do you work when creating a new compound, what's your reasoning behind trying certain structures? (mods: I hope SAR discussion is okay here.. )

 

[Hans Meyer]

K(5HT2A)-values

what would be really interesting is some receptor affinities for your compounds, but I guess this will be difficult to achieve. :/

accomplishing the synthesis of an N-Benzyl-Phenethylamine active in sub-mg doses but without the full agonism (which is the probable reason of the toxicity of the classic NBOMe compounds at least as far as I know) would be quite something!

how do you work when creating a new compound, what's your reasoning behind trying certain structures? (mods: I hope SAR discussion is okay here.. )

Well, for the SAR-questions I go straightforward, study the literature (BRADEN, NICHOLS, SCHULZE-ALEXANDRU...), see what substitutions in which positions cause large effects (5HT2A-equlibrium-konstants) and try to build up new molecules which fullfill the characteristics in structure found in the literature. You are right, I also think the substances with moderate power could be the more psychodelic/psycholytic ones. The K(5HT2A) is IMHO a necessary, but not sufficient condition for beeing psychodelic/psycholytic. You are right, the toxicity corresponds IMHO with high 5HT2A-power (small K-values).

Secondly I am restricted in what my collection of chemicals offer (I am not able to buy chemicals of interest any more, for I am a private person, not a company).

(mods: if this discussion is not ok, please delete it).

So long, Hans

 

[SteamboatBillJr]

If you notice the majority of classical psychedelics bind strongly at receptors other than 5HT2A. LSD actually binds strongest at the 5HT1A receptor. Also, notice the most selective 5HT2a agnoists cause the most fatalities. With the guidance of brilliant neurobiologist we are learning the psychedelic experience is the result of 5HT2A activation in combination with other receptors. With LSD, increased potency and decreased toxicity occur when 5HT1A, 5HT2A, and other receptors are activated in concert.

If you enjoy the medical journals you could get started with this PubMed entry here.
https://www.ncbi.nlm.nih.gov/pubmed/26080602/

 

[Hans Meyer]

5HT1A- besides 5HT2A-agonism

If you notice the majority of classical psychedelics bind strongly at receptors other than 5HT2A. LSD actually binds strongest at the 5HT1A receptor. Also, notice the most selective 5HT2a agnoists cause the most fatalities. With the guidance of brilliant neurobiologist we are learning the psychedelic experience is the result of 5HT2A activation in combination with other receptors. With LSD, increased potency and decreased toxicity occur when 5HT1A, 5HT2A, and other receptors are activated in concert.

If you enjoy the medical journals you could get started with this PubMed entry here.
https://www.ncbi.nlm.nih.gov/pubmed/26080602/

Thanks a lot for that valuable informations. For that I will check the extensive listings of binding affinities found in the literature (to 5HT1A besides the 5HT2A-receptor). What is with antagonism? I read in a discussion, that i.e. some PEA-NBX act as such.

 

[SteamboatBillJr]

I think that each chemical is different and the historical evidence we see tends to exclude the idea all psychedelics work in the same way at the other ones.

My hunch is the full therapeutic effects of LSD involve receptors other than 5HT1A and 5HT2A. Perhaps the majority of most tryptamines effects are from 5HT1A and 5HT2A. LSD's sweet afterglow is unique and really knocks me back differently than the tryptamines I have tested. I think what happens about that afterglow is the reason LSD has the most therapeutic potential in the experiments I do.

Regarding your antagonism question, I am uncertain of how significant that is. I abandoned looking deeper into the NBOMe line of psychedelics people used. The comparatively poor safety of DOX and NOBOMes excluded them from my research. Tryptamines and LSD are the psychedelics I have changed to.

 

[Solipsis]

From what I understand: relatives of high affinity agonists can be antagonists because both bind very strongly to the receptor. The difference with antagonists is that this does not lead to a conformational change in the receptor that leads to activation / signal transduction, or perhaps that there is activation but the antagonist then keeps binding for such a long time with no change that it hogs the binding site and prevents activity in netto.

IIRC some NBX tryptamines were found to be serotonergic antagonists?

 

[Hans Meyer]

Rc

here comes an update of "New research chemicals": file "Table of SV_v2.2.2.1" in:
https://pantorise.net/viewtopic.php?f=17&t=1049&start=30

 

[Solipsis]

Thanks very much

These compounds, like other NBX seem like they might be quite stimulating on the sympathetic nervous system - I applaud that you use titration methods well and effectively find activity in microgram ranges, but taking trimipramine it seems that it obscures the reports usefulness due to possible interaction, and it might be quite dangerous increasing perhaps chance of say seizure or CNS overload...

It's probably lucky (or maybe smart relative to circumstances) that you don't seem to want to explore +++ psychedelic potentials.

 

[Hans Meyer]

Thanks very much

These compounds, like other NBX seem like they might be quite stimulating on the sympathetic nervous system - I applaud that you use titration methods well and effectively find activity in microgram ranges, but taking trimipramine it seems that it obscures the reports usefulness due to possible interaction, and it might be quite dangerous increasing perhaps chance of say seizure or CNS overload...

It's probably lucky (or maybe smart relative to circumstances) that you don't seem to want to explore +++ psychedelic potentials.

Yes I agree. I can not tolerate higher doses any more. Otherwise I would try.

 

[Bigazznugz]

Yes I agree. I can not tolerate higher doses any more. Otherwise I would try.

hey hans do you have any insight on this chemical N,N-diethyl-3-(methyl(1,3,4,5-tetrahydrobenzo[cd]indol-4-yl)amino)propanamide AKA NDTDI?

duration affinities anything?

 

[Hans Meyer]

new molecules

hey hans do you have any insight on this chemical N,N-diethyl-3-(methyl(1,3,4,5-tetrahydrobenzo[cd]indol-4-yl)amino)propanamide AKA NDTDI?

duration affinities anything?

o yeh, that would be a very nice molecule, I guess it would be potent. But: I am not able to build up such substance for my very restricted possibilities.
I can imagine that it was builded up in the past, I try to recherch the literature.
So long, Hans

 

[Solipsis]

For post 107: this would be the structure:

Just use http://opsin.ch.cam.ac.uk/ and copy the image link and put it in between these:

[img]link[/img]

It was discovered that lipophilic compounds of these types have quite high affinity for liver enzymes which are happy to demethylate the 5-position methoxy. So it would probably be worth checking out the less lipophilic ones or use 2C-B-FLY as your parent compound which is available as RC at quite a number of places these days and doesn't have a vulnerable 5-methoxy. But if your sublingual administration is fine then it's not critical...

 

[Hans Meyer]

thank you solipsis! that is a very interesting point of view!
If I understand you right, the meO- is transformed to HO- by the first liver pass, or is it completely removed to H- ?
So the 5-OH derivates shoud be systemically (oral) potent?
The sublingual administration isn´t fine, only a workaraound. Some compounds need several mg, something to much for sublingual admin.

Also thanks for the opsin-link, lateron I will try; now I am in a hurry.
Hans