Archives of Pharmacal Research
- 제9권2호
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- Pages.81-86
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- 1986
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- 0253-6269(pISSN)
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- 1976-3786(eISSN)
Inhibition of hepatic microsomal drug-metabolizing enzymes by imperatorin
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Shin, Kuk-Hyun
(Natural Products Research Institute, Seoul National University) ;
- Woo, Won-Sick (Natural Products Research Institute, Seoul National University)
- 발행 : 1986.06.01
초록
The effect of imperatorin on hepatic microsomal mixed function oxidases (MF0) was investigated. On acute treatment, imperatorin (30 mg/kg, i.p) caused a significant reduction in activities of hepatic aminopyrine N-demethylase, hexobarbital hydroxylase and aniline hydroxylase as well as cytochrome p0450 content in rats and mice. Kinetic studies on rat liver enzymes revealed that imperatorin appeared to be a competitive inhibitor of aminopyrine N-demethylase (Ki,0.007 mM), whereas a non-competitive inhibitor of hexobarbital hydroxylase (Ki, 0.0148 mM). Imperatorin also inhibited non-competitively aniline metabolism (Ki 0.2 mM). Imperatorin binds to phenobarbital-induced cytochrome p-450 to give a typical type 1 binding sepctrum (max. 388nm, min 422 nm). Multiple administrations of imperatorin (30 mg/kg. i. p. daily for 7 days) to mice shortended markedly the duration of hexobarbital narcosis and increased activities of hepatic aminopyrine N-demethylase and hexobarbital hydroxylase and the level of cytochrome p-450 where as aniline hydroxylase activity was unaffected.
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