Integrated structure- and ligand-basedin silicoapproach to predict inhibition of cytochrome P450 2D6

Oxidation of Methoxyphenethylamines by Cytochrome P450 2D6

Cytochrome P450 (P450) 2D6 is involved in the oxidation of a large fraction ( 30%) of drugs used by humans and also catalyzes the O-demethylation of the model substrates 3and 4-methoxyphenethylamine followed by subsequent ring hydroxylation to dopamine. Burst kinetics were not observed; rate-limiting step(s) must occur prior to product formation. Rates of reduction of ferric P450 2D6 were stimu...

Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability.

Enzymatic conversion of hydrocodone to hydromorphone is catalyzed by cytochrome P450 2D6, which is inactive in about 7% of Caucasians [poor metabolizers (PMs)] and can be inhibited by quinidine pretreatment in the remainder [extensive metabolizers (EMs)]. If hydromorphone, having a substantially higher mu-receptor affinity than hydrocodone, contributes importantly to the physiological and subje...

Cytochrome P450 2D6 as a model antigen.

Cytochrome P450 2D6 (CYP2D6) has been identified as the major autoantigen in type 2 autoimmune hepatitis (AIH). However, because of a lack of appropriate animal models, the etiology of AIH is still poorly understood. We generated a mouse model for AIH using the human CYP2D6 as a triggering molecule for autoimmunity. We infected wild-type FVB mice with an adenovirus expressing human CYP2D6 (Ad-2...

EffEct of cytochromE P450 2D6 anD 3a EnzymE InhIbItIon on thE mEtabolIsm of oxycoDonE

Pharmacogenetics of Cytochrome P450 2D6: A Translational Medicine Perspective

With rapid scientific advances in the postgenomic era, pharmacogenomics has developed into an important area of translational medicine research. Pharmacogenetics studies the variability in drug response between different patient genotypes. By using patient genomic information, this bench-to-bedside research approach aims to develop more effective targeting of drug therapy in clinical practice. ...