CYP2D6 | EPFL Graph Search

Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D6, a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, via the addition or removal of certain functional groups – specifically, hydroxylation, demethylation, and dealkylation. CYP2D6 also activates some prodrugs. This enzyme also metabolizes several endogenous substances, such as hydroxytryptamines, neurosteroids, and both m-tyramine and p-tyramine which CYP2D6 metabolizes into dopamine in the brain and liver. Considerable variation exists in the efficiency and amount of CYP2D6 enzyme produced between individuals. Hence, for drugs that are metabolized by CYP2D6 (that is, are CYP2D6 substrates), certain individuals will eliminate these drugs quickly (ultrarapid metabolizers) while others slowly (poor metabolizers). If a drug is metabolized too quickly, it may decrease the drug's efficacy while if the drug is metabolized too slowly, toxicity may result. So, the dose of the drug may have to be adjusted to take into account of the speed at which it is metabolized by CYP2D6. Other drugs may function as inhibitors of CYP2D6 activity or inducers of CYP2D6 enzyme expression that will lead to decreased or increased CYP2D6 activity respectively. If such a drug is taken at the same time as a second drug that is a CYP2D6 substrate, the first drug may affect the elimination rate of the second through what is known as a drug-drug interaction. The gene is located on chromosome 22q13.1. near two cytochrome P450 pseudogenes (CYP2D7P and CYP2D8P). Among them, CYP2D7P originated from CYP2D6 in a stem lineage of great apes and humans, the CYP2D8P originated from CYP2D6 in a stem lineage of Catarrhine and New World monkeys' stem lineage.

Using Negative Control Populations to Assess Unmeasured Confounding and Direct Effects

Mats Julius Stensrud

Sometimes treatment effects are absent in a subgroup of the population. For example, penicillin has no effect on severe symptoms in individuals infected by resistant Staphylococcus aureus, and codeine has no effect on pain in individuals with certain polym ...

Lippincott Williams & Wilkins2024

Highly Sensitive Detection of the Antidepressant Fluoxetine With an Extended Gate Field Effect Transistor

Mihai Adrian Ionescu, Shokoofeh Sheibani

Fluoxetine (FL) is one of the selective serotonin reuptake inhibitors, which is used as an anti-depressant, as well as anti-panic drug. In this work, a sensor for label-free recognition of trace amounts of FL is introduced, which is based on an extended ga ...

IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC2022