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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.
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