Kavion123
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DXM and the Blood-Brain Barrier
Can anyone explain to me how exactly dextromethorphan crosses the blood-brain barrier?
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Hawkguy
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It brings a bunch of rough men with sticks, clubs, and rocks, and they beat away for about an hour before your blood - brain barrier gives in. No just
kidding bro. Is this just out of general curiosity?
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Kavion123
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It is out of general curiosity - I'd expect the DXM molecule to be too large to cross the BBB.
[Edited on 1/13/2015 by Kavion123]
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Bert
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Thread Moved
13-1-2015 at 00:15 |
Chemosynthesis
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Quote: Originally posted by Kavion123  | It is out of general curiosity - I'd expect the DXM molecule to be too large to cross the BBB.
[Edited on 1/13/2015 by Kavion123] |
Why on earth would you consider it too large to cross the BBB? Both fit within pharmacologically active mass profiles of small molecules, and even fit
decently towards suggested drug lead characteristics, which are more stringent. I don't mean this insultingly, but it sounds to me as though as you
just aren't yet educated about such things. I'm also assuming you mean mass when referencing molecular size, so please correct me if you mean surface
area. That gets slightly more nuanced.
Heroin, an example I will continue with later, is a larger opioid and obviously passes. Passing the BBB, or not, or being pumped out depends on a few
factors. One is whether your molecule is actively transported (often p-glycoprotein substrates, as a prototypical example, though there are various
transporters), and another feature that is paramount is the lipophilicity of the drug, since this allows a drug to pass cell membranes rather than
remain in the blood stream.
This is why acetylating morphine twice to heroin increases BBB permeability despite adding bulk to the molecule. De-acetylation on the brain side can
then trap the morphine, by the way. A somewhat analogous aspect with your title compound is the ether formation of the 3-OH, which negates hydrogen
bonding and acidity from the alcohol in dextrorphan. DXM has a predicted logP within 2.9-3.3 vs. DXO's 3.5-3.75. LogS follows expected trends (-3.2
compared to -4.5, respectively). This is all typically far more of a pharmacology topic than even biochemistry, for anyone curious.
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Kavion123
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| Quote: Originally posted by Chemosynthesis |
Why on earth would you consider it too large to cross the BBB? Both fit within pharmacologically active mass profiles of small molecules, and even fit
decently towards suggested drug lead characteristics, which are more stringent. I don't mean this insultingly, but it sounds to me as though as you
just aren't yet educated about such things. I'm also assuming you mean mass when referencing molecular size, so please correct me if you mean surface
area. That gets slightly more nuanced.
Heroin, an example I will continue with later, is a larger opioid and obviously passes. Passing the BBB, or not, or being pumped out depends on a few
factors. One is whether your molecule is actively transported (often p-glycoprotein substrates, as a prototypical example, though there are various
transporters), and another feature that is paramount is the lipophilicity of the drug, since this allows a drug to pass cell membranes rather than
remain in the blood stream.
This is why acetylating morphine twice to heroin increases BBB permeability despite adding bulk to the molecule. De-acetylation on the brain side can
then trap the morphine, by the way. A somewhat analogous aspect with your title compound is the ether formation of the 3-OH, which negates hydrogen
bonding and acidity from the alcohol in dextrorphan. DXM has a predicted logP within 2.9-3.3 vs. DXO's 3.5-3.75. LogS follows expected trends (-3.2
compared to -4.5, respectively). This is all typically far more of a pharmacology topic than even biochemistry, for anyone curious.
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Thank you. I am a beginner on the BBB, as well as pharmacology. I can't get answers like this in real life. Can I private message you when I have
questions?
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Chemosynthesis
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I'm glad my answer was helpful. I understand how difficult it can be to get informative answers on highly technical fields without specializing in
them yourself.
Normally I do not like conversing much in private message, and I cannot promise timely answers depending on my schedule (or even perhaps my
knowledge), but you may certainly private message me with questions, and I appreciate your asking. Hopefully I can be of help and give back to the
community in that sort of regard.
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