Chemistry is the experimental and theoretical study of materials on their properties at both the macroscopic and microscopic levels. 90-64-2, Name is 2-Hydroxy-2-phenylacetic acid, molecular formula is C8H8O3. In an article, author is Amano, Takayuki,once mentioned of 90-64-2, SDS of cas: 90-64-2.
Identification of enzymes responsible for dantrolene metabolism in the human liver: A clue to uncover the cause of liver injury
Dantrolene is used for malignant hyperthermia during anesthesia, and it sometimes causes severe liver injury as a side effect. Dantrolene is metabolized to acetylaminodantrolene, which is formed via the reduction of dantrolene to aminodantrolene and subsequent acetylation. Formation of hydroxylamine during the metabolic process may be associated with liver injury. We identified the enzymes responsible for dantrolene metabolism in humans to elucidate the mechanism of liver injury. Dantrolene reductase activity was not detected in human liver microsomes, but it was detected in cytosol. Formation was increased in the presence of N-1-methylnicotineamide, which is an electron donor to aldehyde oxidase 1 (AOX1). Potent inhibitors of AOX1 and a correlation study with a marker of AOX1 activity, namely phthalazine oxidase activity, in a panel of 28 human liver cytosol samples supported the role of AOX1 in dantrolene reduction. Acetylaminodantrolene formation from aminodantrolene was highly detected in recombinant N-acetyltransferase (NAT) 2 rather than NATI. A glutathione trapping assay revealed the formation of hydroxylamine via an AOX1-dependent reduction of dantrolene but not via hydroxylation of aminodantrolene. In conclusion, we found that AOX1 and NAT2 were responsible for dantrolene metabolism in humans and that AOX1-dependent metabolism determines dantrolene-induced liver injury.
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Reference:
Phthalazine – Wikipedia,
,Phthalazine | C8H6N2 – PubChem