Studies on the glucuronidation of 7-hydroxychlorpromazine in vitro.
The glucuronide of 7-hydroxychlorpromazine (CPOH), formed by incubation with hepatic microsomes and UDP-[U-14C]glucuronic acid, was isolated by extraction into 1-butanol at pH 1 and assayed by liquid scintillation counting. Although concentrations of CPOH greater than 3 X 10(-4) M stimulated its conjugation, the apparent KM of the transferase in microsomes from guinea pig liver for CPOH was 9.5 X 10(-5) M. The apparent activation of glucuronyltransferase by high concentrations of CPOH was prevented when preparations were maximmally stimulated by Triton X-100. The rate of conjugation of CPOH by preparations of guinea pig liver was almost twice that measured with those of rat liver. However, the maximal stimulation of the conjugation of CPOH by Triton with preparations of rat liver was almost twice that observed with microsomes from guinea pig liver. The conjugation of CPOH by microsomes from rat and guinea pig liver was inhibited about 25% by SKF 525-A (1 X 10(-4) M). The inhibitory action of SKF 525-A decreased at concentrations greater than 5 X 10(-4) M and no inhibition was observed at 1 X 10(-3) M.
D000818:Animals; D002746:Chlorpromazine / Q000031:analogs & derivatives* / Q000378:metabolism; D002854:Chromatography, Paper; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005965:Glucuronates / Q000096:biosynthesis; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors
D005965:Glucuronates; D004970:Estrone; D011092:Polyethylene Glycols; D004958:Estradiol; D011335:Proadifen; D002746:Chlorpromazine