Ah, Kaleida ! I think I agree in that sometimes your conclusions are not very conservative, but I love reading your avant-garde SAR studies. Took me some convincing, but you've been adding and adding points in you theory and I think you are into something. It all sounds very coherent.
Haha, yeah, I come up with a lot of my ideas somewhat manicly.... I have a tendency to announce ideas like they are completely earth-shattering but then still ditch them by the next day. This, however, is one I have been working on for quite some time and generally feel more and more confident about the more evidence I find. I'm glad I could get you to at least think about it a bit more seriously, and thanks for the praise as well.
Kaleida have you thought about compiling a tryptamines-themed book with your findings, theories, thoughts etc? I mean, your post above is a chapter in itself lol! It might help in the process of refining and evolving your conclusions.
I have thought it would be really cool to do such a thing, but have never actively planned it in the moment and definitely don't consider myself near experienced enough with these molecules yet to fill an entire book's worth of info and ideas! It certainly would be an interesting way to help organize things though, and I'm sure you're right in that it would help me organize and build upon my thoughts. Thanks much for the idea.
Yeah, I agree ! You've done a whole lot of data mining, if you take it seriously at all - which seems like you do - maybe you should put it out there somewhere !
Thanks again for the encouragement.
It is definitely something I take seriously enough and wouldn't mind putting some of my ideas out when I feel that I've developed them further and gained more experience with these things....
I saw this topic discussed somewhere once before and somebody said that theory doesn't work because tryptamines and lysergamides don't bind to receptors in the same orientation. I don't have a scientific source on that so I admit I can't say for certain whether it's true. You do have some good points, but I'm still not completely convinced. There is just such a huge difference in the trypamine and lysergamide structures. People have tried RU-28306 and NDTDI found them to be garbage and not like tryptamine-lysergamide hybrids. Perhaps the biggest thing going against the theory is that the tryptamine structures aren't constrained. In your pictures comparing MPT to LSD or EPT to ETH-LAD, their structures coincide so closely because you choose draw them in one specific configuration.
Well, with regards to RU-28306 and NDTDI, let's not mistake lack of recreational value for lack of SAR value. Correct me if I'm wrong, but to my knowledge the way that people have found these molecules to be "garbage" is simply that they haven't actually been able to get a psychedelic effect on them, they've either gotten nothing or just like sedation or something.... While I'm not aware of NDTDI ever being scientifically tested as of yet, RU-28306 has been scientifically known as a 5-HT1 and 5-HT2 ligand for decades, with affinity apparently similar to DMT. So, the fact that people have simply not gotten psychedelic effects from it, especially from if I'm not mistaken not particularly DMT-like doses, really doesn't mean anything to me, it pretty much just suggests that either people are just dosing too low or there may be too many off target sites for it to be a good recreational drug due to low potency. Nonetheless, the only way to actually determine whether it or similar molecules fell into the same structure-activity relationships as I was discussing before would be to fully reach its psychedelic effects that it should have and compare it fairly with all the others, and personally I'm willing to bet that it would hold up pretty well given that it's far closer even structurally to the aminotetralins than the tryptamines are.
Personally, I think it's a huge overstatement to say there is a huge difference between the tryptamine and lysergamide structures, and I think their incredibly similar receptor binding patterns across over a dozen or more sites even despite their structural differences and different potencies would suggest that the brain actually is registering them in similar ways quite a lot of the time. With regards to conformations that these molecules take at the receptors, to my knowledge it's mostly all theoretical talk in this area right now regardless of whether people say they're similar or not, but nonetheless I also have seem predictive docking studies that show things such as that LSD has both some binding similarities such as residues forming bonds with the indole rings with both DMT and psilocybin, but also some significantly differences, and fewer similarities to them than they had to one another, though they also had differences from one another not in common with LSD. However, no matter what the truth about that is, I also have to say, with regards to the idea I put forth in my last message, it actually doesn't even matter, at least with regards to 5-HT2A receptor binding which I assume you are talking about... because I was specifically talking about 5-HT1A receptors, which have been much more widely shown to work within this structure-activity relationship that I was fleshing out. When it comes to something like more superficial qualities of a psychedelic experience like the colors and shapes of patterns and such it might be worth arguing that 5-HT2A receptor conformation plays an important role, but as it relates to 5-HT2A receptor being balanced out by 5-HT1A receptor activity, the only requirement is really that it's happening at all.... Ergo, even if we assume that tryptamines and lysergamides actually do bind in entirely different conformations despite arguably having some overlaps in psychedelic strength anyway, it could still be assumed as well that the relationship of LSD, MPT, and 4-HO-MPT compared to ETH-LAD, EPT, and 4-HO-EPT would remain simply on the condition that these molecules do fit that 5-HT1A receptor SAR like I proposed and that simultaneously the progression from MPT to EPT and LSD to ETH-LAD causes either a reduction or no change in 5-HT2A receptor affinity, or if an increase then at least less of an increase than the 5-HT1A increase, thus preserving the relationship that moving from the methyl to the ethyl version of these molecules has of adding in more 5-HT1A activity relative to 5-HT2A activity and producing the consequences of such activity completely indiscriminately of whatever conformation the tryptamines or lysergamides need to take at the 5-HT2A receptor to create their original activity that is balanced out by 5-HT1A. So, in that way even then I could still see the ideas being valid... though I will say that I also still find it more likely that they share some binding properties at both types of receptors as well, but still for me as I said for others this is mostly just theory and assumptions, and I've never been completely convinced of any of this either, it's just ideas.
As for the tryptamines not being constrained, I don't see that as a problem, specifically for the reason that perpetualdawn imagined and Img_9999 scientifically expanded upon. In fact, I think it's also worth noting that the aminotetralins, in addition to being good 5-HT1A receptor agonists, are also potent agonists of dopamine receptors, which I imagine probably has something to do with that conformational constraint that turns the tryptamine molecule into the hybrid phenethylamine molecule that makes up the base of the lysergamide backbone, before having the smaller indole molecule removed to leave the aminotetralin base, though going backwards a step I would also be willing to bet that this relate to why lysergamides have affinity at dopamine receptors in addition to their serotonin receptor affinity. And, notably, while this has been explored less and so you don't see it mentioned so much,
this recent study actually found DMT to have only a bit less dopamine receptor binding affinity than LSD, for instance having twelve times less D2 receptor binding compared to 5-HT2A whereas LSD had about six times less, as might be expected from a molecule (DMT) which is essentially like an aminotetralin but with the phenethylamine backbone made less rigid, whereas psilocin, which actually has its 4-hydroxy group placed in the same place where the phenethylamine backbone would have been, loses even more potency at dopamine receptors but also gains serotonin receptor affinity perhaps for the same reasons, and has seventy-five less D2 affinity overall. So, I just wanted to share that as well to say that, again, even though the ratios of things and their relevance to recreational effects do vary a lot, I do personally see a lot of evidence that these molecules share the same structure-activity relationships overall for a great many things, so I really don't see things like the lack of a more rigid restraint on the tryptamine molecule as a problem so much as I would have in the past anymore....
Yeah it does seem like the tricyclic tryptamines didn't live up to the hopes at all. Too bad.
The cartoon model in my head was that even though the tryptamine structure is unconstrained, that it might orient in the corresponding way to the lysergamide as it docks to the receptor because it fits better that way, and would somehow be in a lower energy state at that "correct" orientation. But I don't have a story for how the somehow part could work. And also I didn't realize/remember that they don't bind in the same orientation as the lysergamide. It's really weird how tryptamine and lysergamide molecules have such a similar structure, and hit much of the same receptors, but do it the other way around from each other. There's a lot of counter intuitive stuff when you dig into the details of things.
Anyways, I'd still be really stoked to try EPT. Maybe I just like those three letters together, an anagram for PET.
That actually was pretty much my understanding of what would happen, though I can't pretend to know too much about that particular topic and it's been a while since I had that explained until now. As I said above, I personally don't necessarily believe that the binding sites are all that different, or that, if they are, that there aren't some other highly analogous structure-activity relationships going on here to explain the highly similar binding profiles nonetheless.
Haha, I actually keep typoing EPT as both PET and ETP when making these posts. Not sure why, it doesn't happen to me with the others.... Anyway, I'd definitely love to hear your thoughts when you do try it, it's unique and certainly will require certain interests but I'm definitely liking it so far.
Yeah, they are unconstrained, but that means that in solution they exist in all possible orientations st different proportions... When they bind on their receptors, they get fixed in the most thermodinamically favourable one.
I dont know how they bind though, and maybe you are right and the amine interacts with different residues in the receptor when we compare tryps vs lysergs.
I think whats more complicated about coming with a unified SAR theory is that phenomenology in the end varies so much between individuals and even between different instances for the same individual.
I do like Kaleidas reasoning though, and I also think that even considering wild variance, each substance seem to have its particular character.
Thanks for the explanation.
And I definitely agree, that's also why I make a big point about saying that it's quite variable and that I may notice some relationships that others don't and vice-versa, for all kinds of reasons we may be variably right or wrong about.... There's really no telling what's going on for sure at this point, it's just fun to try to figure it out.
And thanks again for that, I appreciate the support.
And I also very much agree about that, no matter how versatile the trips can be it's still the same drug you're taking every time, and there are absolutely going to be consistent qualities about the experience, even if they're abstract enough that they're hard to consciously grasp.
I dunno how to put it really. Say I've done DPT at least 20 times, MET 5-6 times, MIPT twice maybe. I've had 4 ho/aco-met numerous times, 4 ho mipt a few times, and 4 aco dpt twice.
As for the MET/MIPT I couldn't really say doing the 4 sub's "HEY, this is fuckin the same same but different". For 4 aco dpt it was like "Oh yeah this is definatly some DPT shit, just a little tamer/different".
Now that could be because I have done DPT more so I am more familiar with it. Also, 100mg 4 aco dpt insulfated could be on par intensity wise with 50mg DPT plugged for me, I just haven't tried that much 4 aco dpt yet. All I know is I get that same weird/playful/anything can happen I'm DPT and I'm gonna fuck with you vibe on both DPT and 4 aco dpt. If that helps, cool. If not, take some yourself! ;-)
That definitely helps, and thanks much for the response.
It is hard to completely relate without personal experience, but that's okay because I'll get around to taking it eventually anyway, hehe.
Actually that's really interesting since I've been working with base tryptamines more, I can definitely relate to what you say about MET and MiPT compared to their 4-subs, I do think that superficially there are some noticeable similarities but not enough that you'd think it was really a similar kind of trip overall, though both have pretty different feels to their counterparts ultimately.... I haven't taken 4-AcO-DPT before but I have taken 4-HO-DPT a couple times and am planning to try DPT soon as well and have been trying to get my head more around it too, so that's actually really interesting to think about by comparison, it definitely makes me a lot more curious to work more with both of these dipropyl chemicals....
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
