Histamine and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline are competitive inhibitors of debrisoquine 4-monooxygenase in rat liver.
The effects of histamine and 1-methyl-6,7-dihydroxy-1,2,3,4- tetrahydroisoquinoline(salsolinol) on debrisoquine 4-monooxygenation, which is catalyzed by cytochrome P-450db 1 (CYP2D1) in rat liver microsomes, were studied. Both histamine and salsolinol competitively inhibited the activity of debrisoquine 4-monooxygenase (Ki = 0.31 and 0.43 mM, respectively). These data demonstrate that histamine and salsolinol bind to the active site of CYP2D1, i.e. histamine and salsolinol have structures (molecular shape) corresponding to the active site of CYP2D1.
Iwahashi
K
K
Department of Psychiatry, Kagawa Medical School, Japan.
Matsuo
Y
Y
Tsuneoka
Y
Y
Ichikawa
Y
Y
Hosokawa
K
K
Suwaki
H
H
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D002384:Catalysis; D019389:Cytochrome P-450 CYP2D6; D065607:Cytochrome P-450 Enzyme Inhibitors; D006632:Histamine / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D065607:Cytochrome P-450 Enzyme Inhibitors; D007546:Isoquinolines; D006632:Histamine; C036617:salsolinol; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6