Metabolism
Aconitine is metabolized by cytochrome P450 isozymes (CYPs). There has been a research in 2011 in China to in-depth investigate the CYPs involved in aconitine metabolism in human liver microsomes. It has been estimated that more than 90 percent of currently available human drug metabolism can be attributed to eight main enzymes (CYP 1A2, 2C9, 2C8, 2C19, 2D6, 2E1, 3A4, 3A5). The researchers used recombinants of these eight different CYPs and incubated it with aconitine. To initiate the metabolism pathway the presence of NADPH was needed. Six CYP-mediated metabolites (M1–M6) were found by liquid-chromatography, these six metabolites were characterized by mass-spectrometry. The six metabolites and the involved enzymes are summarized in the following table:
| Metabolite | Name | Involved CYPs |
|---|---|---|
| M1 | O-Demethyl-aconitine | CYP3A4, CYP3A5, CYP2D6, CYP2C8 |
| M2 | 16-O-Demethyl-aconitine | CYP3A4, CYP3A5, CYP2D6, CYP2C9 |
| M3 | N-deethyl-aconitine | CYP3A4, CYP3A5, CYP2D6, CYP2C9 |
| M4 | O-didemethyl-aconitine | CYP3A5, CYP2D6 |
| M5 | 3-Dehydrogen-aconitine | CYP3A4, CYP3A5 |
| M6 | Hydroxyl-aconitine | CYP3A5, CYP2D6 |
Selective inhibitors where used to determine the involved CYPs in the aconitine metabolism. The results indicate that aconitine was mainly metabolized by CYP3A4, 3A5 and 2D6. CYP2C8 and 2C9 had a minor role to the aconitine metabolism, whereas CYP1A2, 2E1 and 2C19 did not produced any aconitine metabolites at all. The proposed metabolic pathways of aconitine in human liver microsomes and the CYPs involved to it are summarized in the table above.
Read more about this topic: Aconitine
Famous quotes containing the word metabolism:
“He’s got a fifteen percent metabolism with an overactive thyroid and a glandular affectation of about three percent. With a one percent mentality. He’s what we designate as the Crummy Moronic type.”
—Robert Pirosh, U.S. screenwriter, George Seaton, George Oppenheimer, and Sam Wood. Dr. Hugo Z. Hackenbush (Groucho Marx)