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Is there an morphinan that crosses BBB faster than heroin?

N

Neithman

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May 31, 2014
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And is more euphoric than heroin and that has equal effects like say oxymorphone but with a stronger rush and also a warm rush like heroin has?
 
crossing into the brain (having a quick lipid-soluble, but not over lipophilic logarhythmic parition co-efficient) and crossing the BBB (having less affinity for p-glycoprotein than your next opioid, e.g. buprenorphine; which "doesn't cross the blood brain barrier" but is half the strength of fentanyl as a mixed (ant)agonist so "does") are two different factors. The "warm rush" is likely hypothesized to be due to histamine release. I'd wager 3-acetyl-heterocodeine (3-acetyl,6-methyl-morphine) would be a good candidate.
 
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.

As for the original question in the thread, what do you mean by a morphinan? Do you specifically mean morphinans without the 4,5-epoxy bridge or do you mean morphinans generally? One plain morphinan, namely levorphanol, actually takes a good while to start acting even if it's injected intravenously and again, I suppose it has a lot to do with the number of its polar regions, if you compare it to heroin for instance, it's much less polar. If you mean morphinans generally, then you can find a lot of examples of fast-acting opioids like oxymorphone itself, but they're more of research opioids rather than actual drugs in circulation (aside from a few ones like desomorphine which medical use of is scarce or none at the moment, I imagine).
 
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I mean opium derived drugs and the question is which will give the strongest rush with the same quality(euphoric and warm) that heroin has
 
adder said:
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.
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Semantic distinctions; my above response was a roughshod way of saying that crossing into the brain has multiple issues; factors to with with the BBB; lipid penetration; and that factors like histamine do cause subjective differences which are appreciated to different degrees as 'the warm' part of the rush (differing from, many colloquially say, fentanyl, etc.) so I don't see any great difference between what I said and you said, just an outline of how one must get more specific to answer his question to his liking.
 
And desoxymorphine, of course. Permonid, over krokodil form strongly recommended but neither if you want a long, healthy life.
 
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
 
Peel said:
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
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It wouldn't cross the brain faster; 3-MAM is less lipophilic than diacetylmorphine. Also, 3-MAM wouldn't be that potent. The a free 3-phenolic group contributes massively to binding, whereas carbon 6 can accomodate a wide variety of substituents including long alkyl chains and still retain activity. Thus 6-MAM would be a lot more potent than 3-MAM. That is not to say that the acetyl group in 3-MAM will be cleaved in the brain to release morphine. However in terms of direct mu affinity, 6-MAM is the strongest.
 
true - and you can monoacylate but MP goes up so smoking not too good and IV worse. Snorting 50mg dry amps of diamorphine give almost instant results because 3 less stable than 6 (6 has allyl group to displace hydrogen bond acceptor).
 
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