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Morphine: Do CYP2D6 Inhibitors Increase Oral Bioavailability?

Yep, diphen potentiates morphine because it decreases the CYP2D6 enzyme from metabolizing it, so more morphine can make it into your bloodstream intact...as far as I know it doesn't potentiate due to any synergistic effect in the brain (well, except to say that taking both might make you really drowsy).
 
pallidamors said:
Yep, diphen potentiates morphine because it decreases the CYP2D6 enzyme from metabolizing it, so more morphine can make it into your bloodstream intact...as far as I know it doesn't potentiate due to any synergistic effect in the brain (well, except to say that taking both might make you really drowsy).
Click to expand...

Synergy happens in the CNS as well. Both H1 and H2 receptor antagonists are known to be strong potentiators of narcotic analgesia.

This was conclusively shown to be a direct result of antagonism at the H1/H2 receptors (vs secondary mechanism of the drugs being tested) by finding enhanced morphine analgesia in mice with the H1 or H2 receptors knocked out at the genetic level (ref 1, ref 2).

For the record, diphenhydramine is an H1 antagonist.
 
First pass metabolism is a bitch isn't it? :P

Don't waste all that morphine by taking it orally! Booty bump that, its got a bioavailability a little less than IV administration.
 
...ah yeah. Answer to myself:

"Booty bump
Inserting foreign substances inside your rectum for the purpose of absorbing the active ingredients into ones body. using vasoline or another lubricant to coat the outer edge of the rectum in an attempt to soothe the experience is common."
from: www.urbandictionary.com

Thank god, we have the internet. ;)
 
LOL?! It does? ...

Back to the opening question: I have to add that even if CYP2D6 inhibitors increase bioavailability, this does also mean that the compounds toxicity (or better: the toxic sideeffects) is increased, too. For the board members with pharmacological background this may sound rhetorical, but IMHO this gets frequently forgotten.

There is some reason why one shouldn't consume grapefruit juice together with certain pharmaceuticals, just to quote the probably most famous example.

Murphy
 
Morphine is a CYP2D6 Substrate
Click to expand...

Is it? I thought 2D6 was the enzyme that O-demethylates (codeine to morphine, DHC to dihydromorphine etc) and it was 3A4 that was responsible for N-demethylation (and I doubt 2D6 is responsible for conjugation with glucuronic acid - those are the two main metabolic pathways for morphine)
 
Morphine is mainly metabolized by glucuronidation. CYP-enzymes play only a minor role and, thus, inhibition of any CYP will do...not much.

Glucuronidation is accomplished by COMPLETE different enzymes, which do not belong at all to the CYP-family.
Glucuronid-Transferases belong, as the name already says, to the class "transferases", while the CYP-enzymes are "oxidoreductases". See here for an overview. They are not even remotely related and the catalytic mechanism is completely different.

Murphy
 
Isn't a big issue with morphine bioavailability the fact that liver enzymes in the gut can break down the morphine to a large extent before it even gets absorbed?

As far as I know, grapefruit juice might get you up to about 40% bioavailability, but other than that I know of no other way to increase it significantly. I'm not even sure if that works, I mean I've tried it with pod tea but who can say for sure really?
 
I guess that the CYP2D6 demethylates the nitrogen in morphine, thus deactivating the compound... Still, the main fraction gets metabolized by means of glucuronid-conjugation (followed by renal secretion).

One must not forget that morphine-6-glucuronid (in contrary to its pos. 3 congener!!) possesses even greater analgesic properties than morphine. So, it's not all this bad... :)
 
...thanks for clearing that out. So, we were all somehow wrong. :) Good to know!

Edit: except FnB, except FnB, except FnB, except FnB, except FnB, except FnB, except FnB, except FnB... ;)
 
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I think I read that diclofenac inhibits glucuronidation.
So would taking diclofenac with codeine or morphine provide a boost??
 
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