Hi.
I have been using opioids for 10 years and today i found out something interesting.
There are prodrugs and active metabolites, which may or may not contribute to the opioid effects of parent compound. Active metabolites are usually formed via CYP2D6 hepatic enzymes.
Codeine is metabolized into morphine, norcodeine and codeine-6-glucuronide. Morphine is the most potent of these drugs, and contributes to almost all opioid activity of consumed codeine. C-6-G is also active but once u are poor CYP2D6 metaboliser, no morphine is created and consumed codeine won't get u high or act as sufficient analgetic.
Tramadol, beside its NRI and SRI activity, is even more dependent on CYP2D6 activity to act as an opioid because parent compound has extremely low binging to opioid receptors, so without 0-desmethyltramadol it's more like weak SNRI than weak opioid.
Oxycodone, which Is considered to be one of strong opioids, is also prodrug which depends on CYP2D6 to form oxymorphone - metabolite which actually cause most of opioid effects of consumed oxycodone.
And now here Is strange one , Dihydrocodeine. Dihydrocodeine is very close to codeine but approximately twice as potent as both codeine or tramadol and it is also metabolized by CYP2D6 into very active metabolite, dihydromorphine.
But, something strange must be going on because even if your CYP2D6 is completely inhibited by for example bupropion, NDRI antidepressant, dihydrocodeine will be still capable of getting u high or calming your pain.
All of these active metabolites like O-dsmt, morphine, oxymorphone, dihydromorphone are formed in amounts of 1-10% of the amount of consumed prodrug.
Why Is dihydrocodeine active by itself, And oxycodone with much higher affinity rely on its metabolite to produce any effects ? I will also mention that BA of oral DHC is +-20 %, oral BA of oxycodone is 60-80 %. How Is it possible that i can effectively use DHC but other weak opioids or even strong one, Oxycodone, Is not producing any noticable effects ?
I have been using opioids for 10 years and today i found out something interesting.
There are prodrugs and active metabolites, which may or may not contribute to the opioid effects of parent compound. Active metabolites are usually formed via CYP2D6 hepatic enzymes.
Codeine is metabolized into morphine, norcodeine and codeine-6-glucuronide. Morphine is the most potent of these drugs, and contributes to almost all opioid activity of consumed codeine. C-6-G is also active but once u are poor CYP2D6 metaboliser, no morphine is created and consumed codeine won't get u high or act as sufficient analgetic.
Tramadol, beside its NRI and SRI activity, is even more dependent on CYP2D6 activity to act as an opioid because parent compound has extremely low binging to opioid receptors, so without 0-desmethyltramadol it's more like weak SNRI than weak opioid.
Oxycodone, which Is considered to be one of strong opioids, is also prodrug which depends on CYP2D6 to form oxymorphone - metabolite which actually cause most of opioid effects of consumed oxycodone.
And now here Is strange one , Dihydrocodeine. Dihydrocodeine is very close to codeine but approximately twice as potent as both codeine or tramadol and it is also metabolized by CYP2D6 into very active metabolite, dihydromorphine.
But, something strange must be going on because even if your CYP2D6 is completely inhibited by for example bupropion, NDRI antidepressant, dihydrocodeine will be still capable of getting u high or calming your pain.
All of these active metabolites like O-dsmt, morphine, oxymorphone, dihydromorphone are formed in amounts of 1-10% of the amount of consumed prodrug.
Why Is dihydrocodeine active by itself, And oxycodone with much higher affinity rely on its metabolite to produce any effects ? I will also mention that BA of oral DHC is +-20 %, oral BA of oxycodone is 60-80 %. How Is it possible that i can effectively use DHC but other weak opioids or even strong one, Oxycodone, Is not producing any noticable effects ?
