Synthetic Opiates and Cytochrome P450

By Alex

Since the area I am exploring is relatively untouched in the scientific world, it is often difficult to gain a background understanding of the interactions that occur between morphine and the opiate detoxification enzymes. Thankfully, I was able to help gain an understanding of the interactions present in the liver through two papers that analyzed the interactions between the critical cytochrome enzymes and methadone, a synthetic opiate. Though methadone is not identical to morphine, the basics of the interaction are similar enough to get me a little extra important knowledge going into the actual experiments.


The process, in simple terms, begins with the introduction of methadone into bloodstream, which in turn deposits in the liver. The methadone, which attaches to opiate receptors, is then sent to the hepatic portal circulation, where the hepatocytes check the blood for potentially harmful contents. The toxic contents of the liver are then cleaned out and neutralized by enzymes. The cytochromes that deal with methadone specifically are CYP2B6, CYP3A4, and to a lesser degree, CYP2D6.




The methadone is then demethylated, leaving the harmless chemical EDDP, which is expelled in the urine with EMDP, the other result of the demethylation.

The various stages of the demethylation process for methadone.

That’s all the information I currently have on the process, but my research is ongoing, and I hope to come to an deeper understanding soon enough through research and lab work.

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