The in vitro metabolism of hydralazine.
Hydralazine was metabolized in vitro to phthalazine and phthalazine-1-one by microsomal enzymes requiring NADPH. Hydrazine was not detected as a metabolite under these in vitro conditions. Addition of 1-hydrazinophthalazin-4-one, a possible intermediate metabolite, decreased covalent binding to protein but also decreased metabolism. Phthalazine and phthalazin-1-one also decreased covalent binding to protein to a lesser extent. N-Acetylcysteine significantly decreased the level of phthalazine and phthalazin-1-one detected in microsomal incubations. The results are consistent with a reactive intermediate, but not 1-hydrazinophthalazin-4-one, being responsible for both covalent binding and production of phthalazine.
Streeter
A J
AJ
Timbrell
J A
JA
D000818:Animals; D006830:Hydralazine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010793:Phthalazines / Q000378:metabolism*; D011724:Pyridazines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010793:Phthalazines; D011724:Pyridazines; D006830:Hydralazine