The ability of soybean lipoxygenase to mediate the N-demethylation of imipramine and related drugs in the presence of hydrogen peroxide was examined.Under optimal assay conditions,Vmax values of 14 to 18 mol formaldeh...The ability of soybean lipoxygenase to mediate the N-demethylation of imipramine and related drugs in the presence of hydrogen peroxide was examined.Under optimal assay conditions,Vmax values of 14 to 18 mol formaldehyde·min^-1·mol^-1 enzyme were observed.An inhibition of formaldehyde and desipramine formation by nordihydroguaiaretic acid confirmed the lipoxygenase involvement.The blockade of the reaction by glutathione,dithiothreitol butylated hydroxyanisole (BHA) and butylated hydroxytoluene(BHT) indicated the generation of a free radical intermediate from imipramine.Desipramine,trimipramine,clomipramine,and diltiazem,but not amitriptyline and doxepin,were also oxidized,albeit at a lower rate.Collectively,the evidence gathered in this study suggests,for the first time,that tricyclic antidepressant drugs may undergo lipoxygenase-catalyzed N-demethylation.展开更多
文摘The ability of soybean lipoxygenase to mediate the N-demethylation of imipramine and related drugs in the presence of hydrogen peroxide was examined.Under optimal assay conditions,Vmax values of 14 to 18 mol formaldehyde·min^-1·mol^-1 enzyme were observed.An inhibition of formaldehyde and desipramine formation by nordihydroguaiaretic acid confirmed the lipoxygenase involvement.The blockade of the reaction by glutathione,dithiothreitol butylated hydroxyanisole (BHA) and butylated hydroxytoluene(BHT) indicated the generation of a free radical intermediate from imipramine.Desipramine,trimipramine,clomipramine,and diltiazem,but not amitriptyline and doxepin,were also oxidized,albeit at a lower rate.Collectively,the evidence gathered in this study suggests,for the first time,that tricyclic antidepressant drugs may undergo lipoxygenase-catalyzed N-demethylation.
