RoboRobot
Bluelighter
So, I came across a study I hadn't found posted on the enzymes and other possible enzymes methadone is processed / n-demethylated by.
The main one is CYP3A4
Next is: CYP2C8
AND lastly, CYP2D6.
This is in order of most used enzyme to least.
CYP3A4 enzyme's inhabit such a large portion of the liver, though, that they are harder to inhibit.
Now, this IS NOT a thread recommending inhibiting and/or potentiation, but just factual information on where methadone is metabolized (enzyme-wise), and if ever necessary, where to induce or inhibit, plus the link to the cited research report.
To my knowledge, the CYP2C8 would be the hardest to inhibit.
Cimetidine, as many know, inhibits a wide range of Cytochrome P450 (CYP) enzymes.
In this report, it is also noted that paroxetine (Paxil) is a potent CYP2D6 inhibitor.
Fluoxetine and Fluvoxamine also inhibit the said enzyme, showing that many SSRI's have that capability, and also proving that the once said CYP3A4 enzyme being the only one metabolizing methadone is incorrect, as there are higher blood concentrations of R-methadone and S-methadone after dosing with Fluoxetine, fluvoxamine, or paroxetine (in the 14 out of 15 people WITH the CYP2D6 enzyme) which inhibits CYP2D6, proving it has an action in its metabolism.
The report also goes on the describe the differences between (R) and (S) metabolized methadone.
It seems to be well cited as well, though some reports are a bit dated, the good thing about methadone is, we have a long and concrete data history on the substance.
http://dmd.aspetjournals.org/content/31/6/742.full
The main one is CYP3A4
Next is: CYP2C8
AND lastly, CYP2D6.
This is in order of most used enzyme to least.
CYP3A4 enzyme's inhabit such a large portion of the liver, though, that they are harder to inhibit.
Now, this IS NOT a thread recommending inhibiting and/or potentiation, but just factual information on where methadone is metabolized (enzyme-wise), and if ever necessary, where to induce or inhibit, plus the link to the cited research report.
To my knowledge, the CYP2C8 would be the hardest to inhibit.
Cimetidine, as many know, inhibits a wide range of Cytochrome P450 (CYP) enzymes.
In this report, it is also noted that paroxetine (Paxil) is a potent CYP2D6 inhibitor.
Fluoxetine and Fluvoxamine also inhibit the said enzyme, showing that many SSRI's have that capability, and also proving that the once said CYP3A4 enzyme being the only one metabolizing methadone is incorrect, as there are higher blood concentrations of R-methadone and S-methadone after dosing with Fluoxetine, fluvoxamine, or paroxetine (in the 14 out of 15 people WITH the CYP2D6 enzyme) which inhibits CYP2D6, proving it has an action in its metabolism.
The report also goes on the describe the differences between (R) and (S) metabolized methadone.
It seems to be well cited as well, though some reports are a bit dated, the good thing about methadone is, we have a long and concrete data history on the substance.
http://dmd.aspetjournals.org/content/31/6/742.full
