diclofenac potentiates morphine by inhibiting glucuronosyltransferase

[Weltmeister]

https://www.jstage.jst.go.jp/article/dmpk/22/2/22_2_103/_pdf

I just read this study which says that morphine glucuronidation can be prevented by diclofenac. Unless i misread the paper first pass metabolism should be reduced significantly and thus bioavailability increased. Im also assuming that this combo should be relatively safe since its being used in a medical setting already.

I cant think of a reason why people arent using this combo already since dicolfenac is an easy to get OTC medication.

Am i missing something here ?

 

[serotonin2A]

It would actually have the opposite effect. M6G is a potent MOR agonist -- it is significantly more potent than morphine.

 

[aced126]

Even if M6G is more potent than morphine itself in binding, that does not mean a dose of M6G will exert a greater effect than a dose of morphine.

The M6G generated in the liver will not be able to get into the brain, so it will not have a chance to bind onto the brain opioid receptors anyway.

Thus taking diclofenac should potentiate morphine.

On the other hand, if glucuronidation were to take place in the brain, morphine would be a lot more potent than currently is.

 

[serotonin2A]

Even if M6G is more potent than morphine itself in binding, that does not mean a dose of M6G will exert a greater effect than a dose of morphine.

The M6G generated in the liver will not be able to get into the brain, so it will not have a chance to bind onto the brain opioid receptors anyway.

Thus taking diclofenac should potentiate morphine.

On the other hand, if glucuronidation were to take place in the brain, morphine would be a lot more potent than currently is.

I understand why you might think that, but it is not true. M6G can get into the brain from the periphery. It is partially responsible for the analgesia produced by morphine.

https://www.ncbi.nlm.nih.gov/pubmed/1419474
https://www.ncbi.nlm.nih.gov/pubmed/24985077

 

[Weltmeister]

Both M3G and M6G are cleared by the kidneys so theres not much that can be done there. Could there be a way to promote UGT2B7 to metabolise more morphine to M6G instead of M3G ? Well if there is its probably out of my reach.

 

[delphinen]

I realize this is an old thread, but I have been taking Codeine+Diclofenac in high doses lately, and I haven't found any problem nor variation from taking pure Codeine, the experience of the high included -as opposed to Codeine and APAP for example, which very easily makes my stomach feel bad or sick if I take too much.
However, in my mind, if Codeine has to be purchased with another "NSAID" drug in order to be sold legally, I would choose Ibuprofen probably.

 

[Captain.Heroin]

It is not OTC in the US.

 

[Tasker]

It's no longer OTC in the United Kingdom.

 

[Limpet_Chicken]

Codeine? yes it is. fits all changed within the last two days, codeine and DHc are both OTC, although with APAP or ibuprofen,f