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Author: Subject: DXM and the Blood-Brain Barrier
Kavion123
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[*] posted on 12-1-2015 at 20:15
DXM and the Blood-Brain Barrier


Can anyone explain to me how exactly dextromethorphan crosses the blood-brain barrier?
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[*] posted on 12-1-2015 at 20:42


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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[*] posted on 12-1-2015 at 20:51


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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[*] posted on 13-1-2015 at 09:13


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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[*] posted on 13-1-2015 at 10:05


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.


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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[*] posted on 13-1-2015 at 12:22


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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