RT Journal Article
SR Electronic
T1 Metabolism of methimazole by rat liver cytochrome P-450-containing monoxygenases.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 591
OP 600
VO 6
IS 5
A1 P W Lee
A1 R A Neal
YR 1978
UL http://dmd.aspetjournals.org/content/6/5/591.abstract
AB The incubation of methimazole (1-methyl-2-thioimidazole, MMI) with rat hepatic microsomes led to the formation of 3-methyl-2-thiohydantoin and N-methylimidazole. In addition, an NADPH-stimulated binding of 14C and 35S from [14C]- and [35s]MMI to microsomal macromolecules was seen. Both the NADPH-stimulated N-methylimidazole formation and binding of radioactivity from [14C]- and [35S]MMI to microsomal macromolecules appeared to be catalyzed largely by the cytocrhome P-450 to monoxygenase systems of rat hepatic microsomes. A portion of the radioactivity bound to microsomes incubated with [14C]- and [35S]MMI was released as unchanged MMI on prolonged incubation under acid conditions; this suggests that strong binding of MMI to microsomes occurred. A portion of the 35S bound to microsomes incubated with [35S]MMI can be released as 35SCN- on incubation of the 35S-labeled microsomes with CN-. These data suggest that a portion of the sulfur released in the metabolism of MMI to N-methylimidazole is in the form of atomic sulfur (S), which binds to cysteine sulfhydryl groups (R-S-H) in microsomal proteins to form a hydrodisulfide (R-S-S-H).