☛ Official ☚ The Big & Dandy RH-34 Thread
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Solipsis
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Hmm that is weird and interesting..
But let me just point out that lysergamides can break this categorization of 5-HT-2x activity by binding and activating for a long time whereas normally you only have binding and activation for a short time or binding for a long time without activation.
I would want to know more about what suggests this qualifies as an agent capable of causings serotonergic disturbances that are psychedelic and not over-focus on one of these categories too much and rule it out without even getting a chance to judge...
Nevertheless: this RH compound does seem mostly like a ketanserin like drug.
To address the NBOMe issue: afaik current understanding suggests that very selective activity, ANY very selectivity of such a kind that affects supportive systems of vital functions in the body, may be very problematic. Because it may cause an imbalance in the regulation of such a system and cause it to become unable to function such as vascular effects of 5-HT2x on a functional activity level may screw up circulation if you push hard enough and that is what ultrapotent selective agents may be able to do.
In my opinion: be very suspicious of drugs that are both potent and selective as they may upset a balance that is key to a function of the body on another level that is essential to us humans / mammals. Just potency on its own may give us an ability to deal with it by just trying to scale all effects and phenomena involved, just selectivity would mean that an OD requires a lot of material and that kind of thing just does not tend to happen unless someone wants to intentially cause a huge problem... but combine them and all bets are off, perhaps.
But let me just point out that lysergamides can break this categorization of 5-HT-2x activity by binding and activating for a long time whereas normally you only have binding and activation for a short time or binding for a long time without activation.
I would want to know more about what suggests this qualifies as an agent capable of causings serotonergic disturbances that are psychedelic and not over-focus on one of these categories too much and rule it out without even getting a chance to judge...
Nevertheless: this RH compound does seem mostly like a ketanserin like drug.
To address the NBOMe issue: afaik current understanding suggests that very selective activity, ANY very selectivity of such a kind that affects supportive systems of vital functions in the body, may be very problematic. Because it may cause an imbalance in the regulation of such a system and cause it to become unable to function such as vascular effects of 5-HT2x on a functional activity level may screw up circulation if you push hard enough and that is what ultrapotent selective agents may be able to do.
In my opinion: be very suspicious of drugs that are both potent and selective as they may upset a balance that is key to a function of the body on another level that is essential to us humans / mammals. Just potency on its own may give us an ability to deal with it by just trying to scale all effects and phenomena involved, just selectivity would mean that an OD requires a lot of material and that kind of thing just does not tend to happen unless someone wants to intentially cause a huge problem... but combine them and all bets are off, perhaps.
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Aeon Psyche
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even i am not touching this...And that says a lot.
Fertile
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I concluded that with RH-34, Ralf Heim was seeking to further elucidate the QSAR of the NBOMe class. The key takeaway is that the O-methoxy is a requirement (it also overlays the O in the amide of LSD and the lone-pair is in exactly the same orientation), an aromatic (he used benzene and thiophene for those) which I suggest is space-filling a methylene spacer and then a secondary amine and it's lone-pair also overlay the 8-nitrogen of LSD.
So he placed his NBOMe group onto the nitrogen of ring-substituted PEAS (and semi-rigid derivatives such as TCB-2), onto various tryptamines and onto other 5HT2a modulators such as quinazoline-2,4(1H,3H)-dione, a relative of kanaserin.
It seems that the NBOMe modification is only capable of producing partial agonist activity which is interesting.
He and Nichols worked together and now Ralf Heim is working with Nichols. DMBMPP seems to re-enforce the fact that secondary amines are optimal.
It's the biggest step forward in the research of 5HT2a ligands for decades. There is no shortage of other scaffolds the NBOMe modification can be added to but Rale Heim is in the right place. There is decades of work ahead and given his style of development, it will be slow but finely granular.
The fact that know, tested and understood 4HT2 agonists were chosen resulted in the tryptamines and the ring-substituted PEAs, I don't think that the work was primarily aimed at developing a new class of hallucinogen. It's just that you can train an animal to respond to, say 2CB, that's been done, so you can test the NBOMes to see if the subjective effects are the same. Convenience really.
So he placed his NBOMe group onto the nitrogen of ring-substituted PEAS (and semi-rigid derivatives such as TCB-2), onto various tryptamines and onto other 5HT2a modulators such as quinazoline-2,4(1H,3H)-dione, a relative of kanaserin.
It seems that the NBOMe modification is only capable of producing partial agonist activity which is interesting.
He and Nichols worked together and now Ralf Heim is working with Nichols. DMBMPP seems to re-enforce the fact that secondary amines are optimal.
It's the biggest step forward in the research of 5HT2a ligands for decades. There is no shortage of other scaffolds the NBOMe modification can be added to but Rale Heim is in the right place. There is decades of work ahead and given his style of development, it will be slow but finely granular.
The fact that know, tested and understood 4HT2 agonists were chosen resulted in the tryptamines and the ring-substituted PEAs, I don't think that the work was primarily aimed at developing a new class of hallucinogen. It's just that you can train an animal to respond to, say 2CB, that's been done, so you can test the NBOMes to see if the subjective effects are the same. Convenience really.
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BTW also note that depending on the example, the aromatic from which the secondary amine springs can be 2,3 or even 4 methylenes from said aromatic.
I forgot to mention NDTDI, a non-rigid LSD homologue. Notice that the chainfrom the benzene and from the pyrrole are 2 methylenes from the tertiary amine moiety.
For a long time I've considered that the ring-substituted PEAs and the tryptamines bind in exactly the same manner. You may ask why the former uses primary amines while the latter uses tertiary amines (unless the alkyl extends beyond amine). Direction of nitrogen lone-pair.
There are more ideas, but if their is obviously something wrong to this point... I would rather be told than to infer totally flawerd logic.
I forgot to mention NDTDI, a non-rigid LSD homologue. Notice that the chainfrom the benzene and from the pyrrole are 2 methylenes from the tertiary amine moiety.
For a long time I've considered that the ring-substituted PEAs and the tryptamines bind in exactly the same manner. You may ask why the former uses primary amines while the latter uses tertiary amines (unless the alkyl extends beyond amine). Direction of nitrogen lone-pair.
There are more ideas, but if their is obviously something wrong to this point... I would rather be told than to infer totally flawerd logic.