codeine; inactive prodrug?

[djsim]

I undertook a pharmacology prac class yesterday for med school. Now I am a registered pharmacist so I know the stuff pretty well. The experiment was very straight forward; examining the effects of opiate agonists/antagonists on a section of guinea pig ileum prepeared in a 20mL bath. A concentration/dose response curve was recorded with Maclab for morphine, codeine, and naloxone. The point of course is to see the effects of opoid mu receptor (ant)agonists on gastric mobility inhibition (where gastric motility is inversely proportional to opoid receptor activation of course).
The data shows that codeine indeed activates motility inhibition; so obviously the codeine is acting through the opiate receptors...
BUT, I was under the impression that codeine was just a pro-drug to morphine. In other words, without the liver's CYP450 2D6 enzyme, the codeine is not converted to morphine, so is therefore inactive. I realise other CYP450 enzymes come into play too, but for the same reason (the liver isnt present), I cant see this being relevant. I asked the demonstrator and he couldnt help me -- in fact, he wasn't even certain that "10% of a codeine dose is converted to morphine", nor was he aware of its status as a prodrug. In his defence he said he would check up on it.
So, I know this isnt the most advanced question, but what the hell is going on here? Thanks guys,
Sim

 

[MurphyClox]

Codeine has its own activity as well as it is a prodrug for morphine.

 

[djsim]

Also, check my working here...
This guy in the lab class said he went around and drank the rest of the pipette containers of morphine solution.
Solution was concentration of morphine @ 1.0E-3M
Volume in each was approx 400uL, x3 = 1200uL = 1.2mL
Therefore its 1.2E-6 mols of morphine.
And with M(morphine) = 285.4, m(morphine) = 0.343mg, correct?
Cos he swore to god he was nodding off after class and I absolutely call bullshit on this. 8)
Thanks

 

[djsim]

You undertook a pharm class "yesterday" (one day???) and think that you know the stuff pretty well? Well enough to spell opioid as "opoid" several times... Go ahead!

And codeine has its own activity as well as it is a prodrug for morphine.

Um, yeh, the state must believe I know it pretty well too because I work in a pharmacy as a pharmacist. Have done for 3 years. Go figure 8)

 

[haribo1]

If you can find some legal analog of glutethimide, then that would help the body convert morphine->codeine

 

[Limpet_Chicken]

Without the noxious effects on ACTH secretion?
I'm not aware of any.

Now if only I knew of one that caused, rather than inhibited that effect I would be rather pleased.

 

[djsim]

If you can find some legal analog of glutethimide, then that would help the body convert morphine->codeine

OK, I am aware of this (glutethimide is looong gone in Australia though), but for the point in question, it is correct to say that some of codeine's pharmacological activity is not due to the morphine (from the CYP450 2D6 conversion)? I guess when codeine intolerance (due to insufficient cyp450 2d6 levels) is talked about, it means that codeine is not totally ineffective, just partially so.

 

[fastandbulbous]

BilZ0r posted a table of mu receptor affinities in an ADD thread for a shitload of opiates/opioids (including some that acted as prodrugs) many moons ago with respect to this very question. Can't remember where exactly, so you'll have to search yourself