fbpx
Wikipedia

CYP2D6

March 16, 2024

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
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesCYP2D6, CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2, CYP2DL1, CYPIID6, P450-DB1, P450C2D, P450DB1, cytochrome P450 family 2 subfamily D member 6, Cytochrome P450 2D6
External IDsOMIM: 124030 HomoloGene: 133550 GeneCards: CYP2D6
Orthologs
SpeciesHumanMouse
Entrez

1565

n/a

Ensembl

n/a

UniProt

P10635

n/a

RefSeq (mRNA)

NM_000106
NM_001025161

n/a

RefSeq (protein)

NP_000097
NP_001020332

n/a

Location (UCSC)Chr 22: 42.13 – 42.13 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

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]

Gene edit

The gene is located on chromosome 22q13.1. near two cytochrome P450 pseudogenes (CYP2D7P and CYP2D8P).[13] Among them, CYP2D7P originated from CYP2D6 in a stem lineage of great apes and humans,[14] the CYP2D8P originated from CYP2D6 in a stem lineage of Catarrhine and New World monkeys' stem lineage.[15] Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[16]

Genotype/phenotype variability edit

CYP2D6 shows the largest phenotypical variability among the CYPs, largely due to genetic polymorphism. The genotype accounts for normal, reduced, and non-existent CYP2D6 function in subjects. Pharmacogenomic tests are now available to identify patients with variations in the CYP2D6 allele and have been shown to have widespread use in clinical practice.[17] The CYP2D6 function in any particular subject may be described as one of the following:[18]

  • poor metabolizer – little or no CYP2D6 function
  • intermediate metabolizers – metabolize drugs at a rate somewhere between the poor and extensive metabolizers
  • extensive metabolizer – normal CYP2D6 function
  • ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, so greater-than-normal CYP2D6 function occurs

A patient's CYP2D6 phenotype is often clinically determined via the administration of debrisoquine (a selective CYP2D6 substrate) and subsequent plasma concentration assay of the debrisoquine metabolite (4-hydroxydebrisoquine).[19]

The type of CYP2D6 function of an individual may influence the person's response to different doses of drugs that CYP2D6 metabolizes. The nature of the effect on the drug response depends not only on the type of CYP2D6 function, but also on the extent to which processing of the drug by CYP2D6 results in a chemical that has an effect that is similar, stronger, or weaker than the original drug, or no effect at all. For example, if CYP2D6 converts a drug that has a strong effect into a substance that has a weaker effect, then poor metabolizers (weak CYP2D6 function) will have an exaggerated response to the drug and stronger side-effects; conversely, if CYP2D6 converts a different drug into a substance that has a greater effect than its parent chemical, then ultrarapid metabolizers (strong CYP2D6 function) will have an exaggerated response to the drug and stronger side-effects.[20] Information about how human genetic variation of CYP2D6 affects response to medications can be found in databases such PharmGKB,[21] Clinical Pharmacogenetics Implementation Consortium (CPIC).[22]

Genetic basis of variability edit

The variability in metabolism is due to multiple different polymorphisms of the CYP2D6 allele, located on chromosome 22. Subjects possessing certain allelic variants will show normal, decreased, or no CYP2D6 function, depending on the allele. Pharmacogenomic tests are now available to identify patients with variations in the CYP2D6 allele and have been shown to have widespread use in clinical practice.[17] The current known alleles of CYP2D6 and their clinical function can be found in databases such as PharmVar.[23]

CYP2D6 enzyme activity for selected alleles[24][25]
Allele CYP2D6 activity
CYP2D6*1 normal
CYP2D6*2 normal
CYP2D6*3 none
CYP2D6*4 none
CYP2D6*5 none
CYP2D6*6 none
CYP2D6*7 none
CYP2D6*8 none
CYP2D6*9 decreased
CYP2D6*10 decreased
CYP2D6*11 none
CYP2D6*12 none
CYP2D6*13 none
CYP2D6*14 none
CYP2D6*15 none
CYP2D6*17 decreased
CYP2D6*19 none
CYP2D6*20 none
CYP2D6*21 none
CYP2D6*27 normal
CYP2D6*29 decreased
CYP2D6*31 none
CYP2D6*33 normal
CYP2D6*38 none
CYP2D6*40 none
CYP2D6*41 decreased
CYP2D6*42 none
CYP2D6*44 none
CYP2D6*47 none
CYP2D6*50 decreased
CYP2D6*51 none
CYP2D6*68 none
CYP2D6*92 none
CYP2D6*100 none
CYP2D6*101 none
CYP2D6 duplication increased

Ethnic factors in variability edit

Ethnicity is a factor in the occurrence of CYP2D6 variability. The reduction of the liver cytochrome CYP2D6 enzyme occurs approximately in 7–10% in white populations, and is lower in most other ethnic groups such as Asians and African-Americans at 2% each. A complete lack of CYP2D6 enzyme activity, wherein the individual has two copies of the polymorphisms that result in no CYP2D6 activity at all, is said to be about 1-2% of the population.[26] The occurrence of CYP2D6 ultrarapid metabolizers appears to be greater among Middle Eastern and North African populations.[27][28]

Caucasians with European descent predominantly (around 71%) have the functional group of CYP2D6 alleles, producing extensive metabolism, while functional alleles represent only around 50% of the allele frequency in populations of Asian descent.[29]

This variability is accounted for by the differences in the prevalence of various CYP2D6 alleles among the populations–approximately 10% of whites are intermediate metabolizers, due to decreased CYP2D6 function, because they appear to have the one (heterozygous) non-functional CYP2D6*4 allele,[24] while approximately 50% of Asians possess the decreased functioning CYP2D6*10 allele.[24]

Ligands edit

Following is a table of selected substrates, inducers and inhibitors of CYP2D6. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2D6 can be classified by their potency, such as:

  • Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values of sensitive substrates metabolized through CYP2D6, or more than 80% decrease in clearance thereof.[30]
  • Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values of sensitive substrates metabolized through CYP2D6, or 50-80% decrease in clearance thereof.[30]
  • Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values of sensitive substrates metabolized through CYP2D6, or 20-50% decrease in clearance thereof.[30]
Selected inducers, inhibitors and substrates of CYP2D6
Substrates
↑ = bioactivation by CYP2D6		 Inhibitors Inducers

Strong

Moderate

Weak

Unspecified potency

Strong

Unspecified potency

Dopamine biosynthesis edit

Biosynthetic pathways for catecholamines and trace amines in the human brain[62][63][36]
 
In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid phenylalanine. It is well established that dopamine is produced from L-tyrosine via L-dopa; however, recent evidence has shown that CYP2D6 is expressed in the human brain and catalyzes the biosynthesis of dopamine from L-tyrosine via p-tyramine.[36] Similarly, CYP2D6 also metabolizes m-tyramine into dopamine.[36]

References edit

  1. ^ a b c ENSG00000275211, ENSG00000280905, ENSG00000282966, ENSG00000283284, ENSG00000272532 GRCh38: Ensembl release 89: ENSG00000100197, ENSG00000275211, ENSG00000280905, ENSG00000282966, ENSG00000283284, ENSG00000272532 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b Wang 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.
  4. ^ Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". European Journal of Pharmacology. 724: 211–8. doi:10.1016/j.ejphar.2013.12.025. PMID 24374199.
  5. ^ a b Teh 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.
  6. ^ Walko CM, McLeod H (April 2012). "Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment". Pharmacogenomics. 13 (6): 691–7. doi:10.2217/pgs.12.27. PMID 22515611.
  7. ^ Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, Dean L, Kane M (2012). Tramadol Therapy and CYP2D6 Genotype. PMID 28520365.
  8. ^ Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, Dean L, Kane M (2012). Codeine Therapy and CYP2D6 Genotype. PMID 28520350.
  9. ^ Zipursky J, Juurlink DN (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.
  10. ^ Sadhasivam S, Myer CM (July 2012). "Preventing opioid-related deaths in children undergoing surgery". Pain Med. 13 (7): 982–3, author reply 984. doi:10.1111/j.1526-4637.2012.01419.x. PMID 22694279.
  11. ^ Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, Carleton B, Hayden MR, Madadi P, Koren G (May 2012). "More codeine fatalities after tonsillectomy in North American children" (PDF). Pediatrics. 129 (5): e1343–7. doi:10.1542/peds.2011-2538. PMID 22492761. S2CID 14167063. (PDF) from the original on 2 February 2024. Retrieved 2 February 2024.
  12. ^ Prows CA, Zhang X, Huth MM, Zhang K, Saldaña SN, Daraiseh NM, Esslinger HR, Freeman E, Greinwald JH, Martin LJ, Sadhasivam S (May 2014). "Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study". Laryngoscope. 124 (5): 1242–50. doi:10.1002/lary.24455. PMID 24122716. S2CID 5326129.
  13. ^ Ahmad HI, Afzal G, Jamal A, Kiran S, Khan MA, Mehmood K, et al. (2021). "In Silico Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family". BioMed Research International. 2021: 5574789. doi:10.1155/2021/5574789. PMC 8128545. PMID 34046497.
  14. ^ Wang H, Tompkins LM (September 2008). "CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme". Current Drug Metabolism. 9 (7): 598–610. doi:10.2174/138920008785821710. PMC 2605793. PMID 18781911.
  15. ^ Yasukochi Y, Satta Y (2011). "Evolution of the CYP2D gene cluster in humans and four non-human primates". Genes & Genetic Systems. 86 (2): 109–116. doi:10.1266/ggs.86.109. PMID 21670550.
  16. ^ "Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6". from the original on 8 March 2010. Retrieved 3 November 2017.
  17. ^ a b Dinama O, Warren AM, Kulkarni J (August 2014). "The role of pharmacogenomic testing in psychiatry: Real world examples". The Australian and New Zealand Journal of Psychiatry. 48 (8): 778. doi:10.1177/0004867413520050. PMID 24413808. S2CID 206399446.
  18. ^ Bertilsson L, Dahl ML, Dalén P, Al-Shurbaji A (February 2002). "Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs". British Journal of Clinical Pharmacology. 53 (2): 111–22. doi:10.1046/j.0306-5251.2001.01548.x. PMC 1874287. PMID 11851634.
  19. ^ Llerena A, Dorado P, Peñas-Lledó EM (January 2009). "Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity". Pharmacogenomics. 10 (1): 17–28. doi:10.2217/14622416.10.1.17. PMID 19102711.
  20. ^ Lynch T, Price A (August 2007). "The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects". American Family Physician. 76 (3): 391–6. PMID 17708140.
  21. ^ "PharmGKB". PharmGKB. from the original on 3 October 2022. Retrieved 3 October 2022.
  22. ^ "CYP2D6 CPIC guidelines". cpicpgx.org. from the original on 3 October 2022. Retrieved 3 October 2022.
  23. ^ "PharmVar". www.pharmvar.org. from the original on 19 May 2020. Retrieved 15 February 2024.
  24. ^ a b c Droll K, Bruce-Mensah K, Otton SV, Gaedigk A, Sellers EM, Tyndale RF (August 1998). "Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians". Pharmacogenetics. 8 (4): 325–33. doi:10.1097/00008571-199808000-00006. PMID 9731719.
  25. ^ "PharmVar". from the original on 19 May 2020. Retrieved 20 May 2020.
  26. ^ Lilley LL, Harrington S, Snyder JS, Swart B (2007). Pharmacology and the Nursing Process. Toronto: Mosby Elsevier. p. 25. ISBN 9780779699711.
  27. ^ McLellan RA, Oscarson M, Seidegård J, Evans DA, Ingelman-Sundberg M (June 1997). "Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians". Pharmacogenetics. 7 (3): 187–91. doi:10.1097/00008571-199706000-00003. PMID 9241658.
  28. ^ Owen RP, Sangkuhl K, Klein TE, Altman RB (July 2009). "Cytochrome P450 2D6". Pharmacogenet Genomics. 19 (7): 559–62. doi:10.1097/FPC.0b013e32832e0e97. PMC 4373606. PMID 19512959.
  29. ^ Bradford LD (March 2002). "CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants". Pharmacogenomics. 3 (2): 229–43. doi:10.1517/14622416.3.2.229. PMID 11972444.
  30. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bx by bz ca cb cc cd ce cf "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. 2007. from the original on 10 October 2007. Retrieved 25 July 2010. Retrieved in July 2011
  31. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag FASS (drug formulary): Swedish environmental classification of pharmaceuticals 11 June 2002 at the Wayback Machine Facts for prescribers (Fakta för förskrivare), retrieved July 2011
  32. ^ a b Leeder JS (June 2001). "Pharmacogenetics and pharmacogenomics". Pediatric Clinics of North America. 48 (3): 765–81. doi:10.1016/S0031-3955(05)70338-2. PMID 11411304.
  33. ^ "Hydrocodone". Drugbank. from the original on 6 September 2011. Retrieved 14 June 2011.
  34. ^ Hoskins JM, Carey LA, McLeod HL (August 2009). "CYP2D6 and tamoxifen: DNA matters in breast cancer". Nature Reviews. Cancer. 9 (8): 576–86. doi:10.1038/nrc2683. PMID 19629072. S2CID 19501089.
  35. ^ "Wakix pitolisant tablets Prescribing Information" (PDF). Wakix HCP. (PDF) from the original on 11 January 2023. Retrieved 11 January 2023.
  36. ^ a b c d e 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.
  37. ^ Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME (May 2021). "Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis". Scientific Reports. 11 (1): 10851. Bibcode:2021NatSR..1110851V. doi:10.1038/s41598-021-90343-y. PMC 8149637. PMID 34035391.
  38. ^ Shen HW, Jiang XL, Winter JC, Yu AM (October 2010). "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Current Drug Metabolism. 11 (8): 659–666. doi:10.2174/138920010794233495. PMC 3028383. PMID 20942780.
  39. ^ a b "DILTIAZEM HCL CD- diltiazem hydrochloride capsule, coated, extended release". DailyMed. 1 February 2017. from the original on 31 January 2019. Retrieved 31 January 2019.
  40. ^ "NIFEDIPINE EXTENDED RELEASE- nifedipine tablet, extended release". DailyMed. 29 November 2012. from the original on 31 January 2022. Retrieved 1 February 2019.
  41. ^ Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE (June 2005). "Inhibition of CYP2D6 activity by bupropion". Journal of Clinical Psychopharmacology. 25 (3): 226–9. doi:10.1097/01.jcp.0000162805.46453.e3. PMID 15876900. S2CID 24591644.
  42. ^ Fasinu PS, Tekwani BL, Avula B, Chaurasiya ND, Nanayakkara NP, Wang YH, et al. (September 2016). "Pathway-specific inhibition of primaquine metabolism by chloroquine/quinine". Malaria Journal. 15 (1): 466. doi:10.1186/s12936-016-1509-x. PMC 5020452. PMID 27618912.
  43. ^ "Medical Cannabis Adverse Effects & Drug Interactions" (PDF). (PDF) from the original on 14 December 2019. Retrieved 28 October 2019.
  44. ^ Zhao Y, Hellum BH, Liang A, Nilsen OG (June 2015). "Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs". Phytotherapy Research. 29 (6): 825–34. doi:10.1002/ptr.5285. PMID 25640685. S2CID 24002845.
  45. ^ Hermann R, von Richter O (September 2012). "Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions". Planta Medica. 78 (13): 1458–77. doi:10.1055/s-0032-1315117. PMID 22855269.
  46. ^ Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, Xu X, Fang Q, Liang Z, Li B (September 2018). "The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins". Chemico-Biological Interactions. 293: 115–123. Bibcode:2018CBI...293..115F. doi:10.1016/j.cbi.2018.07.022. PMID 30086269. S2CID 206489481.
  47. ^ Zhang W, Ramamoorthy Y, Tyndale RF, Sellers EM (June 2003). "Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro". Drug Metabolism and Disposition. 31 (6): 768–72. doi:10.1124/dmd.31.6.768. PMID 12756210.
  48. ^ a b "Citalopram Oral Solution". Drugs.com. from the original on 8 February 2018. Retrieved 23 January 2018.
  49. ^ "Escitalopram-drug-information". UpToDate. from the original on 28 October 2020. Retrieved 22 May 2019.
  50. ^ a b "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". FDA. 26 May 2021. from the original on 4 November 2020. Retrieved 21 June 2020.
  51. ^ Nevels RM, Weiss NH, Killebrew AE, Gontkovsky ST (July 2013). (PDF). German Journal of Psychiatry: 29–42. Archived from the original (PDF) on 9 April 2018. Retrieved 31 August 2016.
  52. ^ Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD (July 1996). "Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice". Clinical Pharmacology and Therapeutics. 60 (1): 25–33. doi:10.1016/s0009-9236(96)90163-0. PMID 8689808. S2CID 1246705.
  53. ^ Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, et al. (May 1997). "Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression". The Journal of Clinical Investigation. 99 (10): 2545–53. doi:10.1172/jci119439. PMC 508096. PMID 9153299.
  54. ^ Guengerich FP, Brian WR, Iwasaki M, Sari MA, Bäärnhielm C, Berntsson P (June 1991). "Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4". Journal of Medicinal Chemistry. 34 (6): 1838–44. doi:10.1021/jm00110a012. PMID 2061924.
  55. ^ Owen JR, Nemeroff CB (30 May 1998). . Depression and Anxiety. 7 (Suppl 1): 24–32. doi:10.1002/(SICI)1520-6394(1998)7:1+<24::AID-DA7>3.0.CO;2-F. PMID 9597349. S2CID 34832618. Archived from the original on 1 November 2019. Retrieved 1 November 2019.
  56. ^ a b c d FASS, The Swedish official drug catalog > Kodein Recip 19 July 2011 at the Wayback Machine Last reviewed 8 April 2008
  57. ^ He N, Zhang WQ, Shockley D, Edeki T (February 2002). "Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes". European Journal of Clinical Pharmacology. 57 (12): 847–51. doi:10.1007/s00228-001-0399-0. PMID 11936702. S2CID 601644.
  58. ^ Foster BC, Sockovie ER, Vandenhoek S, Bellefeuille N, Drouin CE, Krantis A, et al. (2008). "In Vitro Activity of St. John's Wort Against Cytochrome P450 Isozymes and P-Glycoprotein". Pharmaceutical Biology. 42 (2): 159–69. doi:10.1080/13880200490512034. S2CID 2366709.
  59. ^ Gaudineau C, Auclair K (May 2004). "Inhibition of human P450 enzymes by nicotinic acid and nicotinamide". Biochemical and Biophysical Research Communications. 317 (3): 950–956. doi:10.1016/j.bbrc.2004.03.137. PMID 15081432.
  60. ^ Briguglio M, Hrelia S, Malaguti M, Serpe L, Canaparo R, Dell'Osso B, et al. (December 2018). "Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic/Pharmacodynamic Profiles". Pharmaceutics. 10 (4): 277. doi:10.3390/pharmaceutics10040277. PMC 6321138. PMID 30558213.
  61. ^ Kudo S, Ishizaki T (December 1999). "Pharmacokinetics of haloperidol: an update". Clinical Pharmacokinetics. 37 (6): 435–56. doi:10.2165/00003088-199937060-00001. PMID 10628896. S2CID 71360020.
  62. ^ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacology & Therapeutics. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186.
  63. ^ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.

Further reading edit

  • Smith G, Stubbins MJ, Harries LW, Wolf CR (December 1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
  • Wolf CR, Smith G (1999). "Cytochrome P450 CYP2D6". IARC Scientific Publications (148): 209–29. PMID 10493260.
  • Ding X, Kaminsky LS (2003). "Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts". Annual Review of Pharmacology and Toxicology. 43: 149–73. doi:10.1146/annurev.pharmtox.43.100901.140251. PMID 12171978.
  • Lilienfeld S (2006). "Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease". CNS Drug Reviews. 8 (2): 159–76. doi:10.1111/j.1527-3458.2002.tb00221.x. PMC 6741688. PMID 12177686.
  • Yu AM, Idle JR, Gonzalez FJ (May 2004). "Polymorphic cytochrome P450 2D6: humanized mouse model and endogenous substrates". Drug Metabolism Reviews. 36 (2): 243–77. doi:10.1081/DMR-120034000. PMID 15237854. S2CID 11330784. from the original on 29 June 2022. Retrieved 5 July 2019.
  • Abraham JE, Maranian MJ, Driver KE, Platte R, Kalmyrzaev B, Baynes C, et al. (2010). "CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen". Breast Cancer Research. 12 (4): R64. doi:10.1186/bcr2629. PMC 2949659. PMID 20731819.
  • Abraham JE, Maranian MJ, Driver KE, Platte R, Kalmyrzaev B, Baynes C, et al. (June 2011). "CYP2D6 gene variants and their association with breast cancer susceptibility". Cancer Epidemiology, Biomarkers & Prevention. 20 (6): 1255–8. doi:10.1158/1055-9965.EPI-11-0321. PMID 21527579. S2CID 32846974.

External links edit

  • Flockhart Lab Cyp2D6 Substrates Page at IUPUI
  • Human CYP2D6 genome location and CYP2D6 gene details page in the UCSC Genome Browser.
  • Overview of all the structural information available in the PDB for UniProt: P10635 (Cytochrome P450 2D6) at the PDBe-KB.

March 16, 2024
cyp2d6, cytochrome, p450, enzyme, that, humans, encoded, gene, primarily, expressed, liver, also, highly, expressed, areas, central, nervous, system, including, substantia, nigra, available, structurespdbhuman, uniprot, search, pdbe, rcsblist, codes2f9q, 3qm4,. 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 CYP2D6Available structuresPDBHuman UniProt search PDBe RCSBList of PDB id codes2F9Q 3QM4 3TBG 3TDA 4WNT 4WNU 4WNV 4WNW 4XRY 4XRZIdentifiersAliasesCYP2D6 CPD6 CYP2D CYP2D7AP CYP2D7BP CYP2D7P2 CYP2D8P2 CYP2DL1 CYPIID6 P450 DB1 P450C2D P450DB1 cytochrome P450 family 2 subfamily D member 6 Cytochrome P450 2D6External IDsOMIM 124030 HomoloGene 133550 GeneCards CYP2D6Gene location Human Chr Chromosome 22 human 1 Band22q13 2Start42 126 499 bp 1 End42 130 865 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed inright lobe of liverduodenumsural nerveright uterine tubepituitary glandright lobe of thyroid glandleft lobe of thyroid glandnucleus accumbensanterior pituitaryputamenn aMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functioniron 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 activityCellular componentorganelle membrane endoplasmic reticulum membrane membrane intracellular membrane bounded organelle endoplasmic reticulum mitochondrion cytoplasmBiological processsteroid 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 long chain fatty acid biosynthetic process organic acid metabolic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez1565n aEnsemblENSG00000100197ENSG00000275211ENSG00000280905ENSG00000282966ENSG00000283284ENSG00000272532n aUniProtP10635n aRefSeq mRNA NM 000106NM 001025161n aRefSeq protein NP 000097NP 001020332n aLocation UCSC Chr 22 42 13 42 13 Mbn aPubMed search 2 n aWikidataView Edit HumanCYP2D6 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 Contents 1 Gene 2 Genotype phenotype variability 3 Genetic basis of variability 4 Ethnic factors in variability 5 Ligands 5 1 Dopamine biosynthesis 6 References 7 Further reading 8 External linksGene editThe gene is located on chromosome 22q13 1 near two cytochrome P450 pseudogenes CYP2D7P and CYP2D8P 13 Among them CYP2D7P originated from CYP2D6 in a stem lineage of great apes and humans 14 the CYP2D8P originated from CYP2D6 in a stem lineage of Catarrhine and New World monkeys stem lineage 15 Alternatively spliced transcript variants encoding different isoforms have been found for this gene 16 Genotype phenotype variability editCYP2D6 shows the largest phenotypical variability among the CYPs largely due to genetic polymorphism The genotype accounts for normal reduced and non existent CYP2D6 function in subjects Pharmacogenomic tests are now available to identify patients with variations in the CYP2D6 allele and have been shown to have widespread use in clinical practice 17 The CYP2D6 function in any particular subject may be described as one of the following 18 poor metabolizer little or no CYP2D6 function intermediate metabolizers metabolize drugs at a rate somewhere between the poor and extensive metabolizers extensive metabolizer normal CYP2D6 function ultrarapid metabolizer multiple copies of the CYP2D6 gene are expressed so greater than normal CYP2D6 function occursA patient s CYP2D6 phenotype is often clinically determined via the administration of debrisoquine a selective CYP2D6 substrate and subsequent plasma concentration assay of the debrisoquine metabolite 4 hydroxydebrisoquine 19 The type of CYP2D6 function of an individual may influence the person s response to different doses of drugs that CYP2D6 metabolizes The nature of the effect on the drug response depends not only on the type of CYP2D6 function but also on the extent to which processing of the drug by CYP2D6 results in a chemical that has an effect that is similar stronger or weaker than the original drug or no effect at all For example if CYP2D6 converts a drug that has a strong effect into a substance that has a weaker effect then poor metabolizers weak CYP2D6 function will have an exaggerated response to the drug and stronger side effects conversely if CYP2D6 converts a different drug into a substance that has a greater effect than its parent chemical then ultrarapid metabolizers strong CYP2D6 function will have an exaggerated response to the drug and stronger side effects 20 Information about how human genetic variation of CYP2D6 affects response to medications can be found in databases such PharmGKB 21 Clinical Pharmacogenetics Implementation Consortium CPIC 22 Genetic basis of variability editThe variability in metabolism is due to multiple different polymorphisms of the CYP2D6 allele located on chromosome 22 Subjects possessing certain allelic variants will show normal decreased or no CYP2D6 function depending on the allele Pharmacogenomic tests are now available to identify patients with variations in the CYP2D6 allele and have been shown to have widespread use in clinical practice 17 The current known alleles of CYP2D6 and their clinical function can be found in databases such as PharmVar 23 CYP2D6 enzyme activity for selected alleles 24 25 Allele CYP2D6 activityCYP2D6 1 normalCYP2D6 2 normalCYP2D6 3 noneCYP2D6 4 noneCYP2D6 5 noneCYP2D6 6 noneCYP2D6 7 noneCYP2D6 8 noneCYP2D6 9 decreasedCYP2D6 10 decreasedCYP2D6 11 noneCYP2D6 12 noneCYP2D6 13 noneCYP2D6 14 noneCYP2D6 15 noneCYP2D6 17 decreasedCYP2D6 19 noneCYP2D6 20 noneCYP2D6 21 noneCYP2D6 27 normalCYP2D6 29 decreasedCYP2D6 31 noneCYP2D6 33 normalCYP2D6 38 noneCYP2D6 40 noneCYP2D6 41 decreasedCYP2D6 42 noneCYP2D6 44 noneCYP2D6 47 noneCYP2D6 50 decreasedCYP2D6 51 noneCYP2D6 68 noneCYP2D6 92 noneCYP2D6 100 noneCYP2D6 101 noneCYP2D6 duplication increasedEthnic factors in variability editEthnicity is a factor in the occurrence of CYP2D6 variability The reduction of the liver cytochrome CYP2D6 enzyme occurs approximately in 7 10 in white populations and is lower in most other ethnic groups such as Asians and African Americans at 2 each A complete lack of CYP2D6 enzyme activity wherein the individual has two copies of the polymorphisms that result in no CYP2D6 activity at all is said to be about 1 2 of the population 26 The occurrence of CYP2D6 ultrarapid metabolizers appears to be greater among Middle Eastern and North African populations 27 28 Caucasians with European descent predominantly around 71 have the functional group of CYP2D6 alleles producing extensive metabolism while functional alleles represent only around 50 of the allele frequency in populations of Asian descent 29 This variability is accounted for by the differences in the prevalence of various CYP2D6 alleles among the populations approximately 10 of whites are intermediate metabolizers due to decreased CYP2D6 function because they appear to have the one heterozygous non functional CYP2D6 4 allele 24 while approximately 50 of Asians possess the decreased functioning CYP2D6 10 allele 24 Ligands editFollowing is a table of selected substrates inducers and inhibitors of CYP2D6 Where classes of agents are listed there may be exceptions within the class Inhibitors of CYP2D6 can be classified by their potency such as Strong inhibitor being one that causes at least a 5 fold increase in the plasma AUC values of sensitive substrates metabolized through CYP2D6 or more than 80 decrease in clearance thereof 30 Moderate inhibitor being one that causes at least a 2 fold increase in the plasma AUC values of sensitive substrates metabolized through CYP2D6 or 50 80 decrease in clearance thereof 30 Weak inhibitor being one that causes at least a 1 25 fold but less than 2 fold increase in the plasma AUC values of sensitive substrates metabolized through CYP2D6 or 20 50 decrease in clearance thereof 30 Selected inducers inhibitors and substrates of CYP2D6 Substrates bioactivation by CYP2D6 Inhibitors InducersAll 31 tricyclic antidepressants e g imipramine 30 amitriptyline 30 etc Most 31 SSRIs antidepressant e g fluoxetine 30 paroxetine 30 fluvoxamine 30 venlafaxine 30 31 SNRI antidepressant duloxetine 30 SNRI moderate sensitive substrates of CYP2D6 30 mianserin 31 tetracyclic antidepressant mirtazapine 31 antidepressant opioids codeine 30 31 into morphine 32 tramadol 30 31 into O desmethyltramadol 32 N desmethyltramadol inactive into N O didesmethyltramadol oxycodone 30 hydrocodone into hydromorphone 33 tapentadol antipsychotics e g haloperidol 30 31 risperidone 30 31 perphenazine 30 31 thioridazine 30 31 zuclopenthixol 30 31 iloperidone 30 31 aripiprazole 30 31 chlorpromazine 30 31 levomepromazine 31 remoxipride 31 minaprine 30 RIMA antidepressant tamoxifen 30 31 into hydroxytamoxifen 34 SERM beta blockers metoprolol 30 31 timolol 30 31 alprenolol 30 31 carvedilol 30 bufuralol 30 nebivolol 30 propranolol 30 debrisoquine 30 antihypertensive Class I antiarrhythmics flecainide 30 31 propafenone 30 31 encainide 30 31 mexiletine 30 31 lidocaine 30 sparteine 30 ondansetron 30 31 antiemetic donepezil 30 31 acetylcholinesterase inhibitor phenformin 30 31 antidiabetic tropisetron 31 5 HT3 receptor antagonist stimulants amphetamine 30 methoxyamphetamine 30 dextromethamphetamine 30 Lisdexamfetamine NRI atomoxetine Sensitive substrate of CYP2D6 30 H3 receptor antagonist inverse agonist pitolisant 35 chlorphenamine 30 antihistamine dexfenfluramine 30 serotoninergic anorectic dextromethorphan 30 into dextrorphan antitussive metoclopramide 30 dopamine antagonist perhexiline 30 antianginal agent phenacetin 30 analgesic promethazine 30 antihistamine antiemetic m tyramine 36 p tyramine 36 Lysergic acid diethylamide LSD 37 5 methoxy N N dimethyltryptamine 38 Calcium channel blocker diltiazem minor moderate sensitive substrate 39 nifedipine minor moderate sensitive substrate 40 Strong Certain SSRIs fluoxetine 30 31 paroxetine 30 31 bupropion 30 41 non SSRI antidepressant quinidine 30 31 class I antiarrhythmic agent quinine 42 cinacalcet 30 calcimimetic ritonavir 31 antiretroviral cannabidiol 43 Moderate duloxetine 30 SNRI terbinafine 30 antifungal Weak amiodarone 30 antiarrhythmic berberine 44 45 46 an alkaloid found in plants like berberis buprenorphine 47 in opioid addiction cimetidine 30 H2 receptor antagonist citalopram 30 48 SSRI escitalopram 30 48 49 SSRI fluvoxamine 50 SSRI methylphenidate 51 diltiazem 39 felodipine 52 53 54 mirtazapine 55 sertraline 50 SSRI Unspecified potency antipsychotics haloperidol 56 30 perphenazine 30 56 thioridazine 56 zuclopenthixol 56 chlorpromazine 30 antihistamines H1 receptor antagonists promethazine 57 antipsychotic chlorphenamine 30 diphenhydramine 30 hydroxyzine 30 tripelennamine 30 celecoxib 30 NSAID clemastine 30 antihistamine and anticholinergic clomipramine 30 tricyclic antidepressant cocaine 30 stimulant doxepin 30 tricyclic antidepressant anxiolytic doxorubicin 30 chemotherapeutic halofantrine 30 in malaria hyperforin St Johns Wort 58 levomepromazine 30 antipsychotic methadone 30 analgesic and anti addictive metoclopramide 30 antiemetic prokinetic mibefradil 30 calcium channel blocker midodrine 30 a1 agonist moclobemide 30 antidepressant niacin 59 nicotinic acid and its form niacinamide nicotinamide collectively called as vitamin B3 sesame 60 seeds oil ticlopidine 30 antiplatelet Strong glutethimide hypnotic sedative Unspecified potency haloperidol 61 typical antipsychotic Dopamine biosynthesis edit Biosynthetic pathways for catecholamines and trace amines in the human brain 62 63 36 nbsp L Phenylalanine L Tyrosine L DOPA Epinephrine Phenethylamine p Tyramine Dopamine Norepinephrine N Methylphenethylamine N Methyltyramine p Octopamine Synephrine 3 Methoxytyramine AADC AADC AADC primarypathway PNMT PNMT PNMT PNMT AAAH AAAH brainCYP2D6 minorpathway COMT DBH DBH nbsp In humans catecholamines and phenethylaminergic trace amines are derived from the amino acid phenylalanine It is well established that dopamine is produced from L tyrosine via L dopa however recent evidence has shown that CYP2D6 is expressed in the human brain and catalyzes the biosynthesis of dopamine from L tyrosine via p tyramine 36 Similarly CYP2D6 also metabolizes m tyramine into dopamine 36 References edit a b c ENSG00000275211 ENSG00000280905 ENSG00000282966 ENSG00000283284 ENSG00000272532 GRCh38 Ensembl release 89 ENSG00000100197 ENSG00000275211 ENSG00000280905 ENSG00000282966 ENSG00000283284 ENSG00000272532 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Wang 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 8 doi 10 1016 j ejphar 2013 12 025 PMID 24374199 a b Teh 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 7 doi 10 2217 pgs 12 27 PMID 22515611 Pratt VM Scott SA Pirmohamed M Esquivel B Kattman BL Malheiro AJ Dean L Kane M 2012 Tramadol Therapy and CYP2D6 Genotype PMID 28520365 Pratt VM Scott SA Pirmohamed M Esquivel B Kattman BL Malheiro AJ Dean L Kane M 2012 Codeine Therapy and CYP2D6 Genotype PMID 28520350 Zipursky J Juurlink DN 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 Med 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 Carleton B Hayden MR Madadi P Koren G May 2012 More codeine fatalities after tonsillectomy in North American children PDF Pediatrics 129 5 e1343 7 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 Saldana SN Daraiseh NM Esslinger HR Freeman E Greinwald JH Martin LJ Sadhasivam S May 2014 Codeine related adverse drug reactions in children following tonsillectomy a prospective study Laryngoscope 124 5 1242 50 doi 10 1002 lary 24455 PMID 24122716 S2CID 5326129 Ahmad HI Afzal G Jamal A Kiran S Khan MA Mehmood K et al 2021 In Silico Structural Functional and Phylogenetic Analysis of Cytochrome CYPD Protein Family BioMed Research International 2021 5574789 doi 10 1155 2021 5574789 PMC 8128545 PMID 34046497 Wang H Tompkins LM September 2008 CYP2B6 new insights into a historically overlooked cytochrome P450 isozyme Current Drug Metabolism 9 7 598 610 doi 10 2174 138920008785821710 PMC 2605793 PMID 18781911 Yasukochi Y Satta Y 2011 Evolution of the CYP2D gene cluster in humans and four non human primates Genes amp Genetic Systems 86 2 109 116 doi 10 1266 ggs 86 109 PMID 21670550 Entrez Gene CYP2D6 cytochrome P450 family 2 subfamily D polypeptide 6 Archived from the original on 8 March 2010 Retrieved 3 November 2017 a b Dinama O Warren AM Kulkarni J August 2014 The role of pharmacogenomic testing in psychiatry Real world examples The Australian and New Zealand Journal of Psychiatry 48 8 778 doi 10 1177 0004867413520050 PMID 24413808 S2CID 206399446 Bertilsson L Dahl ML Dalen P Al Shurbaji A February 2002 Molecular genetics of CYP2D6 clinical relevance with focus on psychotropic drugs British Journal of Clinical Pharmacology 53 2 111 22 doi 10 1046 j 0306 5251 2001 01548 x PMC 1874287 PMID 11851634 Llerena A Dorado P Penas Lledo EM January 2009 Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity Pharmacogenomics 10 1 17 28 doi 10 2217 14622416 10 1 17 PMID 19102711 Lynch T Price A August 2007 The effect of cytochrome P450 metabolism on drug response interactions and adverse effects American Family Physician 76 3 391 6 PMID 17708140 PharmGKB PharmGKB Archived from the original on 3 October 2022 Retrieved 3 October 2022 CYP2D6 CPIC guidelines cpicpgx org Archived from the original on 3 October 2022 Retrieved 3 October 2022 PharmVar www pharmvar org Archived from the original on 19 May 2020 Retrieved 15 February 2024 a b c Droll K Bruce Mensah K Otton SV Gaedigk A Sellers EM Tyndale RF August 1998 Comparison of three CYP2D6 probe substrates and genotype in Ghanaians Chinese and Caucasians Pharmacogenetics 8 4 325 33 doi 10 1097 00008571 199808000 00006 PMID 9731719 PharmVar Archived from the original on 19 May 2020 Retrieved 20 May 2020 Lilley LL Harrington S Snyder JS Swart B 2007 Pharmacology and the Nursing Process Toronto Mosby Elsevier p 25 ISBN 9780779699711 McLellan RA Oscarson M Seidegard J Evans DA Ingelman Sundberg M June 1997 Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians Pharmacogenetics 7 3 187 91 doi 10 1097 00008571 199706000 00003 PMID 9241658 Owen RP Sangkuhl K Klein TE Altman RB July 2009 Cytochrome P450 2D6 Pharmacogenet Genomics 19 7 559 62 doi 10 1097 FPC 0b013e32832e0e97 PMC 4373606 PMID 19512959 Bradford LD March 2002 CYP2D6 allele frequency in European Caucasians Asians Africans and their descendants Pharmacogenomics 3 2 229 43 doi 10 1517 14622416 3 2 229 PMID 11972444 a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bx by bz ca cb cc cd ce cf Drug Interactions Cytochrome P450 Drug Interaction Table Indiana University School of Medicine 2007 Archived from the original on 10 October 2007 Retrieved 25 July 2010 Retrieved in July 2011 a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag FASS drug formulary Swedish environmental classification of pharmaceuticals Archived 11 June 2002 at the Wayback Machine Facts for prescribers Fakta for forskrivare retrieved July 2011 a b Leeder JS June 2001 Pharmacogenetics and pharmacogenomics Pediatric Clinics of North America 48 3 765 81 doi 10 1016 S0031 3955 05 70338 2 PMID 11411304 Hydrocodone Drugbank Archived from the original on 6 September 2011 Retrieved 14 June 2011 Hoskins JM Carey LA McLeod HL August 2009 CYP2D6 and tamoxifen DNA matters in breast cancer Nature Reviews Cancer 9 8 576 86 doi 10 1038 nrc2683 PMID 19629072 S2CID 19501089 Wakix pitolisant tablets Prescribing Information PDF Wakix HCP Archived PDF from the original on 11 January 2023 Retrieved 11 January 2023 a b c d e 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 Vizeli P Straumann I Holze F Schmid Y Dolder PC Liechti ME May 2021 Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis Scientific Reports 11 1 10851 Bibcode 2021NatSR 1110851V doi 10 1038 s41598 021 90343 y PMC 8149637 PMID 34035391 Shen HW Jiang XL Winter JC Yu AM October 2010 Psychedelic 5 methoxy N N dimethyltryptamine metabolism pharmacokinetics drug interactions and pharmacological actions Current Drug Metabolism 11 8 659 666 doi 10 2174 138920010794233495 PMC 3028383 PMID 20942780 a b DILTIAZEM HCL CD diltiazem hydrochloride capsule coated extended release DailyMed 1 February 2017 Archived from the original on 31 January 2019 Retrieved 31 January 2019 NIFEDIPINE EXTENDED RELEASE nifedipine tablet extended release DailyMed 29 November 2012 Archived from the original on 31 January 2022 Retrieved 1 February 2019 Kotlyar M Brauer LH Tracy TS Hatsukami DK Harris J Bronars CA Adson DE June 2005 Inhibition of CYP2D6 activity by bupropion Journal of Clinical Psychopharmacology 25 3 226 9 doi 10 1097 01 jcp 0000162805 46453 e3 PMID 15876900 S2CID 24591644 Fasinu PS Tekwani BL Avula B Chaurasiya ND Nanayakkara NP Wang YH et al September 2016 Pathway specific inhibition of primaquine metabolism by chloroquine quinine Malaria Journal 15 1 466 doi 10 1186 s12936 016 1509 x PMC 5020452 PMID 27618912 Medical Cannabis Adverse Effects amp Drug Interactions PDF Archived PDF from the original on 14 December 2019 Retrieved 28 October 2019 Zhao Y Hellum BH Liang A Nilsen OG June 2015 Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs Phytotherapy Research 29 6 825 34 doi 10 1002 ptr 5285 PMID 25640685 S2CID 24002845 Hermann R von Richter O September 2012 Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions Planta Medica 78 13 1458 77 doi 10 1055 s 0032 1315117 PMID 22855269 Feng P Zhao L Guo F Zhang B Fang L Zhan G Xu X Fang Q Liang Z Li B September 2018 The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins Chemico Biological Interactions 293 115 123 Bibcode 2018CBI 293 115F doi 10 1016 j cbi 2018 07 022 PMID 30086269 S2CID 206489481 Zhang W Ramamoorthy Y Tyndale RF Sellers EM June 2003 Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro Drug Metabolism and Disposition 31 6 768 72 doi 10 1124 dmd 31 6 768 PMID 12756210 a b Citalopram Oral Solution Drugs com Archived from the original on 8 February 2018 Retrieved 23 January 2018 Escitalopram drug information UpToDate Archived from the original on 28 October 2020 Retrieved 22 May 2019 a b Drug Development and Drug Interactions Table of Substrates Inhibitors and Inducers FDA 26 May 2021 Archived from the original on 4 November 2020 Retrieved 21 June 2020 Nevels RM Weiss NH Killebrew AE Gontkovsky ST July 2013 Methylphenidate and Its Under recognized Under explained and Serious Drug Interactions A Review of the Literature with Heightened Concerns PDF German Journal of Psychiatry 29 42 Archived from the original PDF on 9 April 2018 Retrieved 31 August 2016 Bailey DG Bend JR Arnold JM Tran LT Spence JD July 1996 Erythromycin felodipine interaction magnitude mechanism and comparison with grapefruit juice Clinical Pharmacology and Therapeutics 60 1 25 33 doi 10 1016 s0009 9236 96 90163 0 PMID 8689808 S2CID 1246705 Lown KS Bailey DG Fontana RJ Janardan SK Adair CH Fortlage LA et al May 1997 Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression The Journal of Clinical Investigation 99 10 2545 53 doi 10 1172 jci119439 PMC 508096 PMID 9153299 Guengerich FP Brian WR Iwasaki M Sari MA Baarnhielm C Berntsson P June 1991 Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P 450 IIIA4 Journal of Medicinal Chemistry 34 6 1838 44 doi 10 1021 jm00110a012 PMID 2061924 Owen JR Nemeroff CB 30 May 1998 New antidepressants and the cytochrome P450 system focus on venlafaxine nefazodone and mirtazapine Depression and Anxiety 7 Suppl 1 24 32 doi 10 1002 SICI 1520 6394 1998 7 1 lt 24 AID DA7 gt 3 0 CO 2 F PMID 9597349 S2CID 34832618 Archived from the original on 1 November 2019 Retrieved 1 November 2019 a b c d FASS The Swedish official drug catalog gt Kodein Recip Archived 19 July 2011 at the Wayback Machine Last reviewed 8 April 2008 He N Zhang WQ Shockley D Edeki T February 2002 Inhibitory effects of H1 antihistamines on CYP2D6 and CYP2C9 mediated drug metabolic reactions in human liver microsomes European Journal of Clinical Pharmacology 57 12 847 51 doi 10 1007 s00228 001 0399 0 PMID 11936702 S2CID 601644 Foster BC Sockovie ER Vandenhoek S Bellefeuille N Drouin CE Krantis A et al 2008 In Vitro Activity of St John s Wort Against Cytochrome P450 Isozymes and P Glycoprotein Pharmaceutical Biology 42 2 159 69 doi 10 1080 13880200490512034 S2CID 2366709 Gaudineau C Auclair K May 2004 Inhibition of human P450 enzymes by nicotinic acid and nicotinamide Biochemical and Biophysical Research Communications 317 3 950 956 doi 10 1016 j bbrc 2004 03 137 PMID 15081432 Briguglio M Hrelia S Malaguti M Serpe L Canaparo R Dell Osso B et al December 2018 Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic Pharmacodynamic Profiles Pharmaceutics 10 4 277 doi 10 3390 pharmaceutics10040277 PMC 6321138 PMID 30558213 Kudo S Ishizaki T December 1999 Pharmacokinetics of haloperidol an update Clinical Pharmacokinetics 37 6 435 56 doi 10 2165 00003088 199937060 00001 PMID 10628896 S2CID 71360020 Broadley KJ March 2010 The vascular effects of trace amines and amphetamines Pharmacology amp Therapeutics 125 3 363 375 doi 10 1016 j pharmthera 2009 11 005 PMID 19948186 Lindemann L Hoener MC May 2005 A renaissance in trace amines inspired by a novel GPCR family Trends in Pharmacological Sciences 26 5 274 281 doi 10 1016 j tips 2005 03 007 PMID 15860375 Further reading editSmith G Stubbins MJ Harries LW Wolf CR December 1998 Molecular genetics of the human cytochrome P450 monooxygenase superfamily Xenobiotica the Fate of Foreign Compounds in Biological Systems 28 12 1129 65 doi 10 1080 004982598238868 PMID 9890157 Wolf CR Smith G 1999 Cytochrome P450 CYP2D6 IARC Scientific Publications 148 209 29 PMID 10493260 Ding X Kaminsky LS 2003 Human extrahepatic cytochromes P450 function in xenobiotic metabolism and tissue selective chemical toxicity in the respiratory and gastrointestinal tracts Annual Review of Pharmacology and Toxicology 43 149 73 doi 10 1146 annurev pharmtox 43 100901 140251 PMID 12171978 Lilienfeld S 2006 Galantamine a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer s disease CNS Drug Reviews 8 2 159 76 doi 10 1111 j 1527 3458 2002 tb00221 x PMC 6741688 PMID 12177686 Yu AM Idle JR Gonzalez FJ May 2004 Polymorphic cytochrome P450 2D6 humanized mouse model and endogenous substrates Drug Metabolism Reviews 36 2 243 77 doi 10 1081 DMR 120034000 PMID 15237854 S2CID 11330784 Archived from the original on 29 June 2022 Retrieved 5 July 2019 Abraham JE Maranian MJ Driver KE Platte R Kalmyrzaev B Baynes C et al 2010 CYP2D6 gene variants association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen Breast Cancer Research 12 4 R64 doi 10 1186 bcr2629 PMC 2949659 PMID 20731819 Abraham JE Maranian MJ Driver KE Platte R Kalmyrzaev B Baynes C et al June 2011 CYP2D6 gene variants and their association with breast cancer susceptibility Cancer Epidemiology Biomarkers amp Prevention 20 6 1255 8 doi 10 1158 1055 9965 EPI 11 0321 PMID 21527579 S2CID 32846974 External links editFlockhart Lab Cyp2D6 Substrates Page at IUPUI PharmGKB Annotated PGx Gene Information for CYP2D6 Human CYP2D6 genome location and CYP2D6 gene details page in the UCSC Genome Browser Overview of all the structural information available in the PDB for UniProt P10635 Cytochrome P450 2D6 at the PDBe KB Portal nbsp Biology Retrieved from https en wikipedia org w index php title CYP2D6 amp oldid 1210535665 Ligands, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.