Involvement of CYP2D6, CYP3A4, and other cytochrome P-450 isozymes in N-dealkylation reactions.
Metabolic N-dealkylation is a commonly observed biotransformation with tertiary and secondary amine drugs and related N-alkylated amides, but surprisingly little is known about the cytochrome P-450 isozymes involved in these dealkylation reactions. In this review, evidence is provided that supports the involvement of various P-450 isozymes, but especially CYP3A4 and other isozymes of the CYP3A subfamily. Although CYP2D6 is generally not considered to be capable of catalyzing the N-dealkylation of basic drugs, some examples of the involvement of this important isozyme in N-dealkylation reactions are identified. Procedures used to identify individual P-450 isozymes involved in N-dealkylation reactions are discussed.
Coutts
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RT
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
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Baker
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GB
D000639:Amitriptyline / Q000378:metabolism; D000818:Animals; D015283:Citalopram / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D003640:Dealkylation; D006801:Humans; D007099:Imipramine / Q000378:metabolism; D007527:Isoenzymes / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000502:physiology*
D007527:Isoenzymes; D015283:Citalopram; D000639:Amitriptyline; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D007099:Imipramine