CYP2D6, CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2, CYP2DL1, CYPIID6, P450-DB1, P450C2D, P450DB1, cytochrome P450 family 2 subfamily D member 6, Cytochrome P450 2D6
External IDs
OMIM: 124030 HomoloGene: 133550 GeneCards: CYP2D6
Gene location (Human)
Chr.
Chromosome 22 (human)[1]
Band
22q13.2
Start
42,126,499 bp[1]
End
42,130,865 bp[1]
RNA expression pattern
Bgee
Human
Mouse (ortholog)
Top expressed in
right lobe of liver
duodenum
sural nerve
right uterine tube
pituitary gland
right lobe of thyroid gland
left lobe of thyroid gland
nucleus accumbens
anterior pituitary
putamen
n/a
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
iron ion binding
metal ion binding
heme binding
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
oxidoreductase activity
aromatase activity
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
steroid hydroxylase activity
monooxygenase activity
Cellular component
organelle membrane
endoplasmic reticulum membrane
membrane
intracellular membrane-bounded organelle
endoplasmic reticulum
mitochondrion
cytoplasm
Biological process
steroid metabolic process
alkaloid metabolic process
coumarin metabolic process
lipid metabolism
isoquinoline alkaloid metabolic process
alkaloid catabolic process
oxidative demethylation
heterocycle metabolic process
negative regulation of binding
monoterpenoid metabolic process
xenobiotic metabolic process
arachidonic acid metabolic process
negative regulation of cellular organofluorine metabolic process
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.[3] 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.[3][4]
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.[5] 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.[6] Individuals who have ultrarapid polymorphism, however, may metabolize prodrugs, such as codeine or tramadol, to potentially fatal levels either through breast milk[7][8][9] such as treating post-cesarian section pain. These drugs may also cause serious toxicity in ultrarapid metabolizer patients when used to treat other post-operative pain, such as after tonsillectomy.[10][11][12] 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.[5]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abWang B, Yang LP, Zhang XZ, Huang SQ, Bartlam M, Zhou SF (2009). "New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme". Drug Metabolism Reviews. 41 (4): 573–643. doi:10.1080/03602530903118729. PMID 19645588. S2CID 41857580.
^Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". European Journal of Pharmacology. 724: 211–218. doi:10.1016/j.ejphar.2013.12.025. PMID 24374199.
^ abTeh LK, Bertilsson L (2012). "Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance". Drug Metabolism and Pharmacokinetics. 27 (1): 55–67. doi:10.2133/dmpk.DMPK-11-RV-121. PMID 22185816.
^Walko CM, McLeod H (April 2012). "Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment". Pharmacogenomics. 13 (6): 691–697. doi:10.2217/pgs.12.27. PMID 22515611.
^Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, et al. (2012). Tramadol Therapy and CYP2D6 Genotype. PMID 28520365.
^Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, et al. (2012). Codeine Therapy and CYP2D6 Genotype. PMID 28520350.
^Zipursky J, Juurlink DN (November 2020). "The Implausibility of Neonatal Opioid Toxicity from Breastfeeding". Clinical Pharmacology and Therapeutics. 108 (5): 964–970. doi:10.1002/cpt.1882. PMID 32378749. S2CID 218535295.
^Sadhasivam S, Myer CM (July 2012). "Preventing opioid-related deaths in children undergoing surgery". Pain Medicine. 13 (7): 982–3, author reply 984. doi:10.1111/j.1526-4637.2012.01419.x. PMID 22694279.
^Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. (May 2012). "More codeine fatalities after tonsillectomy in North American children" (PDF). Pediatrics. 129 (5): e1343–e1347. doi:10.1542/peds.2011-2538. PMID 22492761. S2CID 14167063. Archived (PDF) from the original on 2 February 2024. Retrieved 2 February 2024.
^Prows CA, Zhang X, Huth MM, Zhang K, Saldaña SN, Daraiseh NM, et al. (May 2014). "Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study". The Laryngoscope. 124 (5): 1242–1250. doi:10.1002/lary.24455. PMID 24122716. S2CID 5326129.
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...
involved to a lesser extent, and CYP2D6 and CYP3A4 are not involved. Both doxepin and nordoxepin are hydroxylated mainly by CYP2D6, and both doxepin and nordoxepin...
not resulted in death. Atomoxetine is a substrate for CYP2D6. Concurrent treatment with a CYP2D6 inhibitor such as bupropion, fluoxetine, or paroxetine...
active metabolite of tramadol. Tramadol is demethylated by the liver enzyme CYP2D6 to desmetramadol in the same way as codeine, and so similarly to the variation...
dextromethorphan and thereby increase its circulating concentrations via inhibition of CYP2D6. The combination medicine dextromethorphan/bupropion is approved for major...
patients who are CYP2D6 poor or ultrarapid metabolizers, and selecting an alternative drug or reducing initial dose in patients who are CYP2D6 intermediate...
than oxycodone. Hydrocodone is metabolized by the cytochrome P450 enzymes CYP2D6 and CYP3A4, and inhibitors and inducers of these enzymes can modify hydrocodone...
is metabolized primarily by the cytochrome P450 enzyme CYP2D6. Inhibitors and inducers of CYP2D6 may modify the pharmacokinetics of vortioxetine and necessitate...
"Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17". Drug Metabolism and Disposition. 35 (8): 1292–1300. doi:10...
CYP3A4, CYP2D6, and CYP1A2. Its active metabolite meta-chlorophenylpiperazine (mCPP) is known to be formed by CYP3A4 and metabolized by CYP2D6. Inhibition...
it depends on an individual's genetics. People with specific variants of CYP2D6 enzymes may not produce adequate amounts of the active metabolite (desmetramadol)...
respectively). Nortriptyline is metabolized in the liver by the hepatic enzyme CYP2D6, and genetic variations within the gene coding for this enzyme can affect...
treatment should be based on symptoms. Patients with variant forms of the gene CYP2D6 may not receive full benefit from tamoxifen because of too slow metabolism...
suppressed breathing. Oxycodone is metabolized by the enzymes CYP3A4 and CYP2D6. Therefore, its clearance can be altered by inhibitors and inducers of these...
(and other drugs) or with CYP2D6 inhibitors. As many as 1 in 10 Caucasian people and even more black people are poor CYP2D6 metabolizers and therefore...
liver injury remains unclear, findings suggest that it may be related to a CYP2D6 polymorphism. Most patients overdosing with venlafaxine develop only mild...
5-HT4. Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6. The major metabolites of metoclopramide...
including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. The drug appears to primarily inhibit CYP1A2, CYP2D6, and CYP3A4, of which it is described...
"The Life Raft Group: Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6". "DRUGBANK Online: Cytochrome P-450 Enzyme Inhibitors". "MEDICATIONS METABOLIZED...
receptors. It is converted to morphine by metabolism of CYP2D6 enzymes. Individuals who have lower CYP2D6 activity may not metabolize codeine at all, and will...
however, those taking inhibitors of the liver enzymes CYP2D6 or CYP3A4 – or who are poor CYP2D6 metabolizers – may be at risk for significant prolongation...
citalopram and fluvoxamine. CYP2D6 inhibitors increase aripiprazole concentrations to 2–3 times their normal level. When strong CYP2D6 SSRIs (such as fluoxetine...
moderate inhibitor of CYP2D6 and a substrate for CYP2D6, and hence can inhibit its own metabolism. It can also inhibit the clearance of CYP2D6 substrates such...
vary widely among patients, often as a result of hepatic impairment or CYP2D6 polymorphism. Metoprolol was first made in 1969, patented in 1970, and approved...
levorphanol. Dextrorphan is produced by O-demethylation of dextromethorphan by CYP2D6. Dextrorphan is an NMDA antagonist and contributes to the psychoactive effects...
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