GoKawiilDextroproporphan: An analogue for a better DXM
By: hellboy (zg)
DXM has one of the most complicated pharmacokinetics and I have been fascinated by it since the first time I tried a third plateau dose.
It is an over-the-counter cough medicine, originally supposed to replace codeine due to codeine’s addiction liability and risk of fatal respiratory depression.
It belongs to the morphinan chemical class, meaning it looks very similar to morphine and codeine chemically, but they have completely different effects and mechanisms of action in the brain.
At low doses, it’s very effective for suppressing coughs, but at high doses, it’s a portal to another world. Let me explain what it does.
When it’s consumed, it enters the bloodstream and goes to the liver for first-pass metabolism, like most drugs. Then the liver starts metabolizing it rapidly using the enzyme CYP2D6, turning dextromethorphan into dextrorphan (DXO).
DXO is more lipophilic, meaning it’s attracted to fats and lipids. The brain is all fats and lipids, so DXO crosses the blood-brain barrier very quickly and gets into the brain.
At high doses, some DXM is left behind due to enzyme inhibition, because the enzyme is busy turning DXM into DXO. DXM is active and affects the brain in several ways, but it’s less lipophilic, so it creeps in more slowly.
Now we have two drugs in the brain, and they’re not very similar. The metabolite DXO is a strong NMDA antagonist, like ketamine. It causes strong dissociation at high doses, but the effect is not exactly like ketamine. Why?
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