N&PD Moderators: Skorpio | thegreenhand
You're mixing up something here. What is the difference between "crossing into the brain" and crossing the BBB? I suppose there is none, if a given compound is a Pgp substrate, then it crosses the BBB poorly because it's transferred back by Pgp. Buprenorphine does cross the BBB efficiently, it's norbuprenorphine that is a Pgp substrate and crosses the BBB poorly. However, how fast a compound gets to the brain and exerts its effects is neither simply a result of its lipophilicity nor whether it's a Pgp substrate or not. For a compound to cross the BBB fast, it must also have polar regions/be polarizable, I guess the same goes for leaving the brain, e.g. PCP is lipophilic but it doesn't get polarized much if you compare it to compounds that bear electron-donating or electron-withdrawing substituents on aryl rings or have otherwise groups with clear electron-donating or electron-withdrawing properties, as a result it stays quite long in the brain and the effects wear off over a long period of time. On top of that once in the bloodstream drugs get bound to proteins which further complicates their onset of action and how much of a dose can actually exert the effect at a time. I can't get into details as I'm not trained in pharmacology, but it's definitely much more complex than you're painting it and quite different as well.
Also, the opioid rush is hardly due to histamine release, whether someone using opioids likes some itching or not is a different thing (which may just be a result of associating itching with pleasurable effects). Actually, the more euphoric opioids release less histamine vs. the magnitude of opioid effect than morphine, including heroin which is basically metabolized to morphine and 6-MAM, so it's essentially a prodrug that makes the active drug exert less side effects vs. desired effects.
If by heroin you're referring to di-actylmorphine, then, yes, 3-monoactylmorphine would cross the BBB faster than heroin and also be more euphoric
If by heroin you're referring to di-actylmorphine, then, yes, 3-monoactylmorphine would cross the BBB faster than heroin and also be more euphoric