Goerz G, Bolsen K, Vardarman E, Rominger K L
Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Fed. Rep. of Germany.
Arzneimittelforschung. 1993 Dec;43(12):1309-12.
Effects of different doses of clonidine (CAS 4205-90-7) (15, 150, or 300 micrograms/kg body weight) over a period of 3, 14, or 64 days on the activities of delta-aminolevulinic acid synthase (ALA-S) and the P450 dependent isoenzymes aminopyrine-N-demethylase (ADM), 7-ethoxycoumarin-O-deethylase (7-ECO-D), and 7-ethoxyresorufin-O-deethylase (7-ERO-D) as well as on the hepatic porphyrin and P450 content were studied in female rats. Additionally, the urinary excretion of total porphyrins, and porphyrin precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) and the plasma clonidine level were measured. No changes in the activity of ALA-S and in the hepatic and urinary porphyrin, ALA and PBG contents were observed. An increase in the activities of ADM in the short and median term application of clonidine and of 7-ERO-D in the long term application was detected. It is concluded from these findings that clonidine has no effect on the porphyrin biosynthesis, but has an influence on the activities of P450 dependent isoenzymes ADM or 7-ERO-D.
研究了不同剂量可乐定(化学物质登记号4205 - 90 - 7)(15、150或300微克/千克体重)在3、14或64天内对雌性大鼠δ-氨基乙酰丙酸合成酶(ALA - S)以及细胞色素P450依赖的同工酶氨基比林 - N - 脱甲基酶(ADM)、7 - 乙氧基香豆素 - O - 脱乙基酶(7 - ECO - D)和7 - 乙氧基试卤灵 - O - 脱乙基酶(7 - ERO - D)活性的影响,以及对肝脏卟啉和细胞色素P450含量的影响。此外,还测定了总卟啉、卟啉前体δ-氨基乙酰丙酸(ALA)和胆色素原(PBG)的尿排泄量以及血浆可乐定水平。未观察到ALA - S活性以及肝脏和尿液中卟啉、ALA和PBG含量的变化。检测到短期和中期应用可乐定时ADM活性增加,长期应用时7 - ERO - D活性增加。从这些研究结果得出结论,可乐定对卟啉生物合成无影响,但对细胞色素P450依赖的同工酶ADM或7 - ERO - D的活性有影响。