4 ms·

I honestly cannot tell if you are trolling now, but I'll oblige one last time. In good faith, I think you might be oversimplifying the situation a bit. The bind

I honestly cannot tell if you are trolling now, but I'll oblige one last time. In good faith, I think you might be oversimplifying the situation a bit. The binding of psilocin (or any other ligand) to its receptor is not just about the presence or absence of a particular functional group such as the OH group. The entire structure and dynamics of the molecule, including its overall conformation and the spatial orientation of its functional groups all play crucial roles in how it interacts with the receptor. In the case of psilocin, the 4-hydroxyl group does not act alone, but is rather a part of the larger molecule. Apart from it's induction effects with the indole ring, this group has been shown to form a very unique intramolecular hydrogen bond with the distal amine that significantly influences the overall conformation of the drug, and this in turn affects how the drug binds to and activates the receptor. Remarkably, this intramolecular hydrogen bond is largely responsible for many of the unique pharmacological and physical properties of psilocin. ( https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202200183 https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002... ) Moreover, receptors like 5HT2A do not interact with their ligands in a one-size-fits-all manner. Rather, they have unique, intricate 'lock-and-key' or 'induced-fit' relationships with each ligand, where the spatial orientation of every atom matters. Hence, just because a molecule has an OH group doesn't automatically qualify it to bind with the 5HT2A receptor; it needs to have the right molecular structure and conformation. Lastly, while the OH group constitutes a small percentage of the overall molecule, its position and the way it influences the conformation of the psilocin molecule cannot be overlooked. Drug-receptor interactions are not solely dictated by the size or quantity of a particular group, but by the precise alignment of these molecular features. This is the reason even minute changes in the structure of a drug can dramatically alter its pharmacological activity.

amts 3y ago
I'm not trolling, this probably is some effect of the psychoactives' field itself and thinking about it. I am researching the topic about how signalling molecules find their intra- and extracellular targets amongst multiple potential "distractions" along their way. What you describe as 'lock-and-key' or 'induced-fit' relationship is established only at the direct contact of a ligand with the receptor. While the ligand in vivo if not injected locally first needs to move fast through vast distances (relative to its size) until it reaches the receptor. It seems that it is just accepted for granted, as if the ligand "knew" where the receptor is. Your link and explanation are very informative, it seems like this intramolecular hydrogen bond completes a "virtual" third heterocycle in the whole molecule. While senolytic quercetin, for example, also has 3 benzene rings. There's a doctor in my contacts who weighs heavily on heterocycles due to the delocalized electron they contain.

amts 3y ago

I'm not trolling, this probably is some effect of the psychoactives' field itself and thinking about it. I am researching the topic about how signalling molecules find their intra- and extracellular targets amongst multiple potential "distractions" along their way. What you describe as 'lock-and-key' or 'induced-fit' relationship is established only at the direct contact of a ligand with the receptor. While the ligand in vivo if not injected locally first needs to move fast through vast distances (relative to its size) until it reaches the receptor. It seems that it is just accepted for granted, as if the ligand "knew" where the receptor is. Your link and explanation are very informative, it seems like this intramolecular hydrogen bond completes a "virtual" third heterocycle in the whole molecule. While senolytic quercetin, for example, also has 3 benzene rings. There's a doctor in my contacts who weighs heavily on heterocycles due to the delocalized electron they contain.