Dingell J V, Sossi N
Drug Metab Dispos. 1977 Jul-Aug;5(4):397-404.
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.
7-羟基氯丙嗪（CPOH）与肝微粒体及UDP-[U-14C]葡萄糖醛酸一起温育形成的葡萄糖醛酸苷，通过在pH 1条件下用1-丁醇萃取进行分离，并通过液体闪烁计数法进行测定。尽管CPOH浓度大于3×10(-4) M时会刺激其结合反应，但豚鼠肝微粒体中转移酶对CPOH的表观米氏常数（KM）为9.5×10(-5) M。当制剂被Triton X-100最大程度刺激时，高浓度CPOH对葡萄糖醛酸转移酶的表观激活作用被阻止。豚鼠肝制剂对CPOH的结合速率几乎是大鼠肝制剂测定值的两倍。然而，Triton对大鼠肝制剂CPOH结合反应的最大刺激作用几乎是豚鼠肝微粒体观察值的两倍。大鼠和豚鼠肝微粒体对CPOH的结合反应被SKF 525-A（1×10(-4) M）抑制约25%。SKF 525-A在浓度大于5×10(-4) M时抑制作用减弱，在1×10(-3) M时未观察到抑制作用。
