Dihydrocodeine metabolites and agonist activity

[funkee]

Apparently, DHC acts as an agonist, and does not demethylate into dihydromorphine, as per:

Vol. 281, Issue 3, 1164-1170, 1997
Analgesia by Dihydrocodeine Is Not Due to Formation of Dihydromorphine: Evidence from Nociceptive Activity in Rat Thalamus

Ilmar Jurna, Wolfgang Kömen, Joseph Baldauf and Wolfgang Fleischer

Abstract: http://jpet.aspetjournals.org/cgi/content/abstract/281/3/1164

contradicting:

Affinities of dihydrocodeine and its metabolites to opioid receptors.

Schmidt H, Vormfelde S, Klinder K, Gundert-Remy U, Gleiter CH, Skopp G, Aderjan R, Fuhr U

Abstract: http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=12420793&dopt=Abstract

Although the second implies a study on humans, something seems out of place if I'm understanding these
Does anyone have any insight into this?

 

[fastandbulbous]

Rats have a different metabolism to humans, so they may well not demethylate dihydrocodeine (rats can eat MPTP with no ill effects, people get a whiff of it and develop severe Parkinsons disease); humans on the other hand most certainly do as people of certain races have a much greater chance of having an isoform of CYP2D6 that will not O-demethylate codeine & dihydrocodeine. In these people, codeine & dihydrocodeine are absolutely useless as painkillers. Implication - dihydromorphine is very important in DHC's analgesic activity (you also get dihydromorphine-6-glucuronate as in the urine of people taking DHC)

 

[BilZ0r]

^ Um, that ones not quite right F&B... DHC is the more active component in DHC analgesia, as demonstrated by the low plasma concentrations of DHM formed during normal use, and the fact that CYP2D6 poor-metabolizers get just the same analgesia from DHC as regular people [1.

For a detailed discussion of this topic in general, check out my post Opioids as prodrugs.

 

[fastandbulbous]

^ Not the same as it is for codeine then? I know it's (codeine) activity is dependant on 2D6.

At least the bit about the rats & DHM-6-glucuronide actually being present as a metabolite was correct!