From what I understand this is the case with ritalin vs cocaine. Ritalin has a stronger binding affinity compared to cola, but cocaine's large clunky structure allows it to pass the BBB much easier.
Can someone also clarify this for me. Off topic but small tangents are ok here and there if it has a purpose I say. Anywho, when I look at a chemical structure, psychoactive ones obviously, and I focus on what groups are attached to where, I have come to this very crude and probably wrong conclusion to how it actually is but I'll shoot and be informed.
When I look at lets say amphetamine, the benzene ring is pointing left, the amine on the right, the electronegative cloud over the benzene isn't "concentrated" or instead a low density electronegative force spread thinly across this ring. The charge density over the benzene in my mind is what gives amphetamine/methamphetamine some, but minor effect on serotogenic systems. The star of the show is what's going on over on the amine side. I picture the Nitrogen's unpaired electrons as having a relatively good affinity for whatever binding sites are responsible for its dopamine/NE activity. The methylated version makes it so that instead of the two hydrogen atoms rotating about the N, the methyl group makes the amine group a little less prone to spinning around the nitrogen, causing the unpaired electrons to be a little more focused and directed electronegativity, as a result being more selective for that receptor. Would the methyl group make it more lipophilic to the same receptor, allowing it to penetrate a lipid more easily and reach/bind to its receptor? Or is the methyl group alone responsible for the increased potency? The methylated amine causes the compound to have a higher affinity for serotonin if I'm not mistaken, and I picture this as a result of the amine group on the other end being a little less mobile and stable, making the electron cloud around benzene more stable.
Now when you look at MDMA/MDA, you have that dimethoxy bridge focusing a giant chunk of the structures electronegativity to the benzene end of the molecule. I imagine the bridge as being a sort of 'knife' or more like a better fitting ligand to serotogenic receptors, and as a result, the star of the show is now the empathogenic character brought on about the increased affinity to those receptors responsible. Is the dopamine receptor's affinity ofset by the heavy electronegative pull on the other end? Because although there is clearly dopamine acting its part in the show, I wonder if serotogenic activity overpowers the effects of the amine or if there is some loss of activity. I'd say its the latter considering getting to sleep after MDMA is worlds easier than it's base methamphetamine structure.
Then with 4-fluoroamphetamine, there is a flourine attached to the benzene end, again causing a more dense concentration of electrons in that area. The effects then exhibit definite empathy/rolling feel due to a more electronegative benzene, should then cause the increased serotogenic effects, but slightly less dopamine activity was noticed compared to its amphetamine backbone, so again, putting the chemical into a new unique balance of activity. Now I go back and think, does that -CH2- in the dimethoxy add a lipophilic aspect to that electronegative knife provided by the oxygens, almost as a sort of sharper point to that knife, allowing for better cross into membranes or reaching its target receptors. And I'll end this with 5/6-APB. These two compounds replace either oxygen in MDA for a methylene group so it seems like it lost electronegativity, but it's much more lipohilic, perhaps accounting for the longer action than its illegal analogues, would the increase in lipohilic tendencies at that end contribute to the more obvious psychadelic qualities(because looking at the trptamines, theyre kinda bulky and less elegant looking than the PEA's but maybe the high concentration of lipohilic properties along with any -OH, -MeO, -AcO play the role of psychadelic effects? The nitrogen in the indole is also a lot more tensed or I'd say, less stable arrangement compared to the PEA's, hence little DA activity, but still some NE activity?
Also look at the difference between 5-apb and 6-apb. The only difference between the two is where the oxygen was replaced my the methylene, so the action is still serotogenic but because it can linger around longer, the visuals and psychadelic headspace play a role. I've read that people mix 5/6-apb and are the first few RC's to come anywhere close to an MDxx replacement(a stupid notion or at least a wrongfully guided attempt to recreate an experience of one chemical by a different one, which by default sounds pointless) and are even showing to be on the same level as MDMA/MDA, some people preferring it. I personally prefer MDA over MDMA anyday, not that I dislike it but MDMA is a little too gentle for me, unless I most likely have just been getting crappy actual MDMA and decent MDA, or I just lucked out and got good MDMA when I thought it was MDA. Doubt its the case because whenever I seek out molly, I specifically ask if the roll feels more intense, sensual, euphoric, and a little more 'naughty' than whats usual, oh and the visuals are quite nice, infact a bonus. I started my drug use with psychadelia, weed for a few years before technically, and even if it has psy properties they're subtle at the most, but that's like the same reaction you get when you explain to some people that ethanol is a drug and the flip a shit.