View source for CYP2D6

{{Short description|Human liver enzyme}}
{{Use dmy dates|date=December 2023}}
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{{Infobox_gene}}
'''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 [[xenobiotic]]s in the body. In particular, CYP2D6 is responsible for the metabolism and [[clearance (medicine)|elimination]] of approximately 25% of clinically used drugs, via the addition or removal of certain [[functional group]]s&nbsp;– specifically, [[hydroxylation]], [[demethylation]], and [[dealkylation]].<ref name="pmid19645588">{{cite journal | vauthors = Wang B, Yang LP, Zhang XZ, Huang SQ, Bartlam M, Zhou SF | title = New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme | journal = Drug Metabolism Reviews | volume = 41 | issue = 4 | pages = 573–643 | year = 2009 | pmid = 19645588 | doi = 10.1080/03602530903118729 | s2cid = 41857580 }}</ref>  CYP2D6 also activates some [[prodrug]]s. This enzyme also metabolizes several endogenous substances, such as [[N,N-Dimethyltryptamine]], [[serotonin|hydroxytryptamines]], [[neurosteroid]]s, and both [[m-tyramine|''m''-tyramine]] and [[tyramine|''p''-tyramine]] which CYP2D6 metabolizes into [[dopamine]] in the brain and liver.<ref name="pmid19645588"/><ref name="Brain CYP2D6">{{cite journal | vauthors = Wang X, Li J, Dong G, Yue J | title = The endogenous substrates of brain CYP2D | journal = European Journal of Pharmacology | volume = 724 | pages = 211–218 | date = February 2014 | pmid = 24374199 | doi = 10.1016/j.ejphar.2013.12.025 }}</ref><ref name="Good et al 2023">
{{cite journal |
vauthors = Good M, Joel Z, Benway T, Routledge C, Timmermann C, Erritzoe D, Weaver R, Allen G, Hughes C, Topping H, Bowman A, James E |
title = Pharmacokinetics of N,N-dimethyltryptamine in Humans | journal = European Journal of Drug Metabolism and Pharmaco Kinetics | doi = 10.1007/s13318-023-00822-y | date = 2023-04-22 |
volume = 48 |
issue = 3 |
pages = 311–327 | pmid = 37086340 | pmc = 10122081}}</ref>

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 [[enzyme substrate|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#Pharmacology|efficacy]] while if the drug is metabolized too slowly, toxicity may result.<ref name="pmid22185816"/>  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.<ref name="pmid22515611">{{cite journal | vauthors = Walko CM, McLeod H | title = Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment | journal = Pharmacogenomics | volume = 13 | issue = 6 | pages = 691–697 | date = April 2012 | pmid = 22515611 | doi = 10.2217/pgs.12.27 }}</ref> Individuals who exhibit an ultrarapid metabolizer phenotype, metabolize [[prodrug]]s, such as [[codeine]] or [[tramadol]], more rapidly, leading to higher than therapeutic levels.<ref name="pmid28520365">{{cite book|pmid=28520365 |date=2012 |title=Tramadol Therapy and CYP2D6 Genotype | vauthors = Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, Dean L, Kane M }}</ref><ref name="pmid28520350">{{cite book|pmid=28520350 |date=2012 |title=Codeine Therapy and CYP2D6 Genotype | vauthors = Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, Dean L, Kane M }}</ref> A case study of the death of an infant breastfed by an ultrarapid metabolizer mother taking codeine impacted postnatal pain relief clinical practices, but was later debunked.<ref name="pmid32378749">{{cite journal | vauthors = Zipursky J, Juurlink DN | title = The Implausibility of Neonatal Opioid Toxicity from Breastfeeding | journal = Clinical Pharmacology and Therapeutics | volume = 108 | issue = 5 | pages = 964–970 | date = November 2020 | pmid = 32378749 | doi = 10.1002/cpt.1882 | s2cid = 218535295 }}</ref> These drugs may also cause serious toxicity in ultrarapid metabolizer patients when used to treat other post-operative pain, such as after [[tonsillectomy]].<ref name="pmid22694279">{{cite journal | vauthors = Sadhasivam S, Myer CM | title = Preventing opioid-related deaths in children undergoing surgery | journal = Pain Medicine | volume = 13 | issue = 7 | pages = 982–3; author reply 984 | date = July 2012 | pmid = 22694279 | doi = 10.1111/j.1526-4637.2012.01419.x | doi-access = free }}</ref><ref name="pmid22492761">{{cite journal | vauthors = Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, Carleton B, Hayden MR, Madadi P, Koren G | title = More codeine fatalities after tonsillectomy in North American children | journal = Pediatrics | volume = 129 | issue = 5 | pages = e1343–e1347 | date = May 2012 | pmid = 22492761 | doi = 10.1542/peds.2011-2538 | url = https://publications.aap.org/pediatrics/article-pdf/129/5/e1343/896222/peds_2011-2538.pdf | access-date = 2 February 2024 | url-status = live | s2cid = 14167063 | archive-url = https://web.archive.org/web/20240202144200/https://publications.aap.org/pediatrics/article-pdf/129/5/e1343/896222/peds_2011-2538.pdf | archive-date = 2 February 2024 }}</ref><ref name="pmid24122716">{{cite journal | vauthors = Prows CA, Zhang X, Huth MM, Zhang K, Saldaña SN, Daraiseh NM, Esslinger HR, Freeman E, Greinwald JH, Martin LJ, Sadhasivam S | title = Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study | journal = The Laryngoscope | volume = 124 | issue = 5 | pages = 1242–1250 | date = May 2014 | pmid = 24122716 | doi = 10.1002/lary.24455 | s2cid = 5326129 }}</ref> Other drugs may function as [[enzyme inhibitor|inhibitor]]s of CYP2D6 activity or [[inducer]]s 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 interaction|drug-drug interaction]].<ref name="pmid22185816">{{cite journal | vauthors = Teh LK, Bertilsson L | title = Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance | journal = Drug Metabolism and Pharmacokinetics | volume = 27 | issue = 1 | pages = 55–67 | year = 2012 | pmid = 22185816 | doi = 10.2133/dmpk.DMPK-11-RV-121 }}</ref>

== Gene ==

The gene is located on [[chromosome 22]]q13.1. near two cytochrome P450 [[pseudogene]]s (CYP2D7P and CYP2D8P).<ref>{{cite journal | vauthors = Ahmad HI, Afzal G, Jamal A, Kiran S, Khan MA, Mehmood K, Kamran Z, Ahmed I, Ahmad S, Ahmad A, Hussain J, Almas S | title = ''In Silico'' Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family | journal = BioMed Research International | volume = 2021 | pages = 5574789 | date = 2021 | pmid = 34046497 | pmc = 8128545 | doi = 10.1155/2021/5574789 | doi-access = free }}</ref> Among them, CYP2D7P originated from CYP2D6 in a stem lineage of great apes and humans,<ref>{{cite journal | vauthors = Wang H, Tompkins LM | title = CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme | journal = Current Drug Metabolism | volume = 9 | issue = 7 | pages = 598–610 | date = September 2008 | pmid = 18781911 | pmc = 2605793 | doi = 10.2174/138920008785821710 }}</ref> the CYP2D8P originated from CYP2D6 in a stem lineage of [[Catarrhine]] and [[New World monkey]]s' stem lineage.<ref>{{cite journal | vauthors = Yasukochi Y, Satta Y | title = Evolution of the CYP2D gene cluster in humans and four non-human primates | journal = Genes & Genetic Systems | volume = 86 | issue = 2 | pages = 109–116 | date = 2011 | pmid = 21670550 | doi = 10.1266/ggs.86.109 | doi-access = free }}</ref> [[alternative splicing|Alternatively spliced]] transcript variants encoding different [[isoform]]s have been found for this gene.<ref>{{cite web| title = Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1565| access-date = 3 November 2017| archive-date = 8 March 2010| archive-url = https://web.archive.org/web/20100308050423/http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1565| url-status = live}}</ref>

== Genotype/phenotype variability ==

CYP2D6 shows the largest [[phenotype|phenotypical]] variability among the CYPs, largely due to [[genetics|genetic]] [[polymorphism (biology)|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.<ref name="PMID24413808" />
The CYP2D6 function in any particular subject may be described as one of the following:<ref name="pmid11851634">{{cite journal | vauthors = Bertilsson L, Dahl ML, Dalén P, Al-Shurbaji A | title = Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs | journal = British Journal of Clinical Pharmacology | volume = 53 | issue = 2 | pages = 111–122 | date = February 2002 | pmid = 11851634 | pmc = 1874287 | doi = 10.1046/j.0306-5251.2001.01548.x }}</ref>
* 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).<ref name="pmid19102711">{{cite journal | vauthors = Llerena A, Dorado P, Peñas-Lledó EM | title = Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity | journal = Pharmacogenomics | volume = 10 | issue = 1 | pages = 17–28 | date = January 2009 | pmid = 19102711 | doi = 10.2217/14622416.10.1.17 }}</ref>

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.<ref name="pmid17708140">{{cite journal | vauthors = Lynch T, Price A | title = The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects | journal = American Family Physician | volume = 76 | issue = 3 | pages = 391–396 | date = August 2007 | pmid = 17708140 }}</ref> Information about how human genetic variation of CYP2D6 affects response to medications can be found in databases such PharmGKB,<ref>{{cite web |title=PharmGKB |url=https://www.pharmgkb.org/gene/PA128/prescribingInfo |access-date=3 October 2022 |website=PharmGKB |language=en |archive-date=3 October 2022 |archive-url=https://web.archive.org/web/20221003090823/https://www.pharmgkb.org/gene/PA128/prescribingInfo |url-status=live }}</ref> Clinical Pharmacogenetics Implementation Consortium (CPIC).<ref>{{cite web |title=CYP2D6 CPIC guidelines |url=https://cpicpgx.org/gene/cyp2d6/ |access-date=3 October 2022 |website=cpicpgx.org |language=en-US |archive-date=3 October 2022 |archive-url=https://web.archive.org/web/20221003084825/https://cpicpgx.org/gene/cyp2d6/ |url-status=live }}</ref>

== Genetic basis of variability ==

The variability in metabolism is due to multiple different [[Gene polymorphism|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.<ref name="PMID24413808">{{cite journal | vauthors = Dinama O, Warren AM, Kulkarni J | title = The role of pharmacogenomic testing in psychiatry: Real world examples | journal = The Australian and New Zealand Journal of Psychiatry | volume = 48 | issue = 8 | pages = 778 | date = August 2014 | pmid = 24413808 | doi = 10.1177/0004867413520050 | s2cid = 206399446 }}</ref> The current known alleles of CYP2D6 and their clinical function can be found in databases such as PharmVar.<ref>{{Cite web |title=PharmVar |url=https://www.pharmvar.org/gene/CYP2D6 |access-date=2024-02-15 |website=www.pharmvar.org |archive-date=19 May 2020 |archive-url=https://web.archive.org/web/20200519021852/https://www.pharmvar.org/gene/CYP2D6 |url-status=live }}</ref>

== Ethnic factors in variability ==

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 people|white]] populations, and is lower in most other ethnic groups such as [[Asian people|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.<ref>{{cite book|title=Pharmacology and the Nursing Process | vauthors = Lilley LL, Harrington S, Snyder JS, Swart B |publisher=Mosby Elsevier|year=2007|isbn=9780779699711|location=Toronto|pages=25}}</ref> The occurrence of CYP2D6 ultrarapid metabolizers appears to be greater among [[Middle East]]ern and [[North Africa]]n populations.<ref name="pmid9241658">{{cite journal | vauthors = McLellan RA, Oscarson M, Seidegård J, Evans DA, Ingelman-Sundberg M | title = Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians | journal = Pharmacogenetics | volume = 7 | issue = 3 | pages = 187–191 | date = June 1997 | pmid = 9241658 | doi = 10.1097/00008571-199706000-00003 }}</ref><ref name="pmid19512959">{{cite journal | vauthors = Owen RP, Sangkuhl K, Klein TE, Altman RB | title = Cytochrome P450 2D6 | journal = Pharmacogenetics and Genomics | volume = 19 | issue = 7 | pages = 559–562 | date = July 2009 | pmid = 19512959 | pmc = 4373606 | doi = 10.1097/FPC.0b013e32832e0e97 }}</ref> In [[Ethiopia]], a particularly high percentage (30%) of the population are ultrametabolizers. As a result, the analgesic codeine is banned in Ethiopia due to the high rate of adverse events associated with ultrarapid metabolism of codeine in this population.<ref>{{cite journal | vauthors = Baker JL, Shriner D, Bentley AR, Rotimi CN | title = Pharmacogenomic implications of the evolutionary history of infectious diseases in Africa | journal = The Pharmacogenomics Journal | volume = 17 | issue = 2 | pages = 112–120 | date = March 2017 | pmid = 27779243 | pmc = 5380847 | doi = 10.1038/tpj.2016.78 }}</ref>

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.<ref name="pmid11972444">{{cite journal | vauthors = Bradford LD | title = CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants | journal = Pharmacogenomics | volume = 3 | issue = 2 | pages = 229–243 | date = March 2002 | pmid = 11972444 | doi = 10.1517/14622416.3.2.229 }}</ref>

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,<ref name="Droll_1998">{{cite journal | vauthors = Droll K, Bruce-Mensah K, Otton SV, Gaedigk A, Sellers EM, Tyndale RF | title = Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians | journal = Pharmacogenetics | volume = 8 | issue = 4 | pages = 325–333 | date = August 1998 | pmid = 9731719 | doi = 10.1097/00008571-199808000-00006 }}</ref> while approximately 50% of Asians possess the decreased functioning ''CYP2D6*10'' allele.<ref name="Droll_1998" />

== Ligands ==
Following is a table of selected [[enzyme substrate|substrates]], [[enzyme induction and inhibition|inducers]] and [[enzyme induction and inhibition|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 (pharmacology)|potency]], such as:
* '''Strong inhibitor''' being one that causes at least a 5-fold increase in the plasma [[area under the curve (pharmacokinetics)|AUC values]] of sensitive substrates metabolized through CYP2D6, or more than 80% decrease in [[clearance (medicine)|clearance]] thereof.<ref name=Flockhart/>
* '''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.<ref name=Flockhart/>
* '''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.<ref name=Flockhart/>

{| class="wikitable" width=100%
|+'''Selected inducers, inhibitors and substrates of CYP2D6'''
|-
! Substrates<br />↑ <small>= [[bioactivation]] by CYP2D6</small> !! Inhibitors !! Inducers
|- style="vertical-align: top;"
|<!--substrates-->
* All<ref name=FASS/> [[tricyclic antidepressants]], e.g.
** [[imipramine]]<ref name=Flockhart/>
** [[amitriptyline]]<ref name=Flockhart/>
** etc.
* Most<ref name=FASS/> [[SSRI]]s (antidepressant), e.g.
** [[fluoxetine]]<ref name=Flockhart/>
** [[paroxetine]]<ref name=Flockhart/>
** [[fluvoxamine]]<ref name=Flockhart/>
* [[venlafaxine]]<ref name=Flockhart/><ref name=FASS/> ([[serotonin-norepinephrine reuptake inhibitor|SNRI]] antidepressant)
* [[duloxetine]]<ref name=Flockhart/> ([[serotonin-norepinephrine reuptake inhibitor|SNRI]], moderate sensitive substrates of CYP2D6<ref name=Flockhart/>)
* [[mianserin]]<ref name=FASS/> ([[tetracyclic antidepressant]])
* [[mirtazapine]]<ref name=FASS/> ([[antidepressant]])
* [[opioids]]
** [[codeine]]<ref name=Flockhart/><ref name=FASS/> [[bioactivation|↑]] [into [[morphine]]]<ref name=Leeder>{{cite journal | vauthors = Leeder JS | title = Pharmacogenetics and pharmacogenomics | journal = Pediatric Clinics of North America | volume = 48 | issue = 3 | pages = 765–781 | date = June 2001 | pmid = 11411304 | doi = 10.1016/S0031-3955(05)70338-2 }}</ref>
** [[tramadol]]<ref name=Flockhart/><ref name=FASS/> [[bioactivation|↑]] [into [[O-desmethyltramadol]]]<ref name=Leeder/>
** [[N-desmethyltramadol]] [inactive] [[bioactivation|↑]] [into N,O-didesmethyltramadol]
** [[oxycodone]]<ref name=Flockhart/> '''[[Bioactivation|↑]]''' [into [[oxymorphone]]]
** [[hydrocodone]] [[bioactivation|↑]] [into [[hydromorphone]]]<ref>{{cite web |url= http://www.drugbank.ca/drugs/DB00956 |title= Hydrocodone |publisher= Drugbank |access-date= 14 June 2011 |archive-date= 6 September 2011 |archive-url= https://web.archive.org/web/20110906061646/http://www.drugbank.ca/drugs/DB00956 |url-status= live }}</ref>
** [[tapentadol]]
* [[antipsychotics]], e.g.
** [[clopixol]]<ref name=Flockhart/><ref name=FASS/><ref>{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/20946203/ | pmid=20946203 | date=2010 | title=Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies | journal=Acta Psychiatrica Scandinavica | volume=122 | issue=6 | pages=444–453 | doi=10.1111/j.1600-0447.2010.01619.x | vauthors = Davies SJ, Westin AA, Castberg I, Lewis G, Lennard MS, Taylor S, Spigset O }}</ref>
** [[haloperidol]]<ref name=Flockhart/><ref name=FASS/>
** [[risperidone]]<ref name=Flockhart/><ref name=FASS/>
** [[perphenazine]]<ref name=Flockhart/><ref name=FASS/>
** [[thioridazine]]<ref name=Flockhart/><ref name=FASS/>
** [[zuclopenthixol]]<ref name=Flockhart/><ref name=FASS/>
** [[iloperidone]]<ref name=Flockhart/><ref name=FASS/>
** [[aripiprazole]]<ref name=Flockhart/><ref name=FASS/>
** [[chlorpromazine]]<ref name=Flockhart/><ref name=FASS/>
** [[levomepromazine]]<ref name=FASS/>
** [[remoxipride]]<ref name=FASS/>
* [[minaprine]]<ref name=Flockhart/> ([[reversible inhibitor of MAO-A|RIMA]] antidepressant)
* [[tamoxifen]]<ref name=Flockhart/><ref name=FASS/> [[bioactivation|↑]] [into [[hydroxytamoxifen]]]<ref name="pmid19629072">{{cite journal | vauthors = Hoskins JM, Carey LA, McLeod HL | title = CYP2D6 and tamoxifen: DNA matters in breast cancer | journal = Nature Reviews. Cancer | volume = 9 | issue = 8 | pages = 576–586 | date = August 2009 | pmid = 19629072 | doi = 10.1038/nrc2683 | s2cid = 19501089 }}</ref> ([[selective estrogen receptor modulator|SERM]])
* [[beta-blockers]]
** [[metoprolol]]<ref name=Flockhart/><ref name=FASS/>
** [[timolol]]<ref name=Flockhart/><ref name=FASS/>
** [[alprenolol]]<ref name=Flockhart/><ref name=FASS/>
** [[carvedilol]]<ref name=Flockhart/>
** [[bufuralol]]<ref name=Flockhart/>
** [[nebivolol]]<ref name=Flockhart/>
** [[propranolol]]<ref name=Flockhart/>
* [[debrisoquine]]<ref name=Flockhart/> ([[antihypertensive]])
* Class I [[antiarrhythmics]]
** [[flecainide]]<ref name=Flockhart/><ref name=FASS/>
** [[propafenone]]<ref name=Flockhart/><ref name=FASS/>
** [[encainide]]<ref name=Flockhart/><ref name=FASS/>
** [[mexiletine]]<ref name=Flockhart/><ref name=FASS/>
** [[lidocaine]]<ref name=Flockhart/>
** [[sparteine]]<ref name=Flockhart/>
* [[ondansetron]]<ref name=Flockhart/><ref name=FASS/> ([[antiemetic]])
* [[donepezil]]<ref name=Flockhart/><ref name=FASS/> ([[acetylcholinesterase inhibitor]])
* [[phenformin]]<ref name=Flockhart/><ref name=FASS/> ([[antidiabetic]])
* [[tropisetron]]<ref name=FASS/> ([[5-HT3 receptor antagonist]])
* [[stimulants]]
** [[amphetamine]]<ref name=":0">{{cite journal | vauthors = Kraemer T, Maurer HH | title = Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives | journal = Therapeutic Drug Monitoring | volume = 24 | issue = 2 | pages = 277–289 | date = April 2002 | pmid = 11897973 | doi = 10.1097/00007691-200204000-00009 | ref = amph }}</ref>
** [[dextroamphetamine]]<ref name=":0" /> (active metabolite of [[lisdexamfetamine]]<ref>{{cite journal | vauthors = Ermer JC, Pennick M, Frick G | title = Lisdexamfetamine Dimesylate: Prodrug Delivery, Amphetamine Exposure and Duration of Efficacy | journal = Clinical Drug Investigation | volume = 36 | issue = 5 | pages = 341–356 | date = May 2016 | pmid = 27021968 | pmc = 4823324 | doi = 10.1007/s40261-015-0354-y }}</ref>)
** [[levoamphetamine]]<ref name=":0" />
** [[methamphetamine]]<ref name=":0" />
** [[dextromethamphetamine]]<ref name=":0" />
** [[Levmetamfetamine|levomethamphetamine]]<ref name=":0" />
** [[3,4-Methylenedioxyamphetamine|3,4-methylenedioxyamphetamine]]<ref name=":0" />
** [[3,4-Methylenedioxyamphetamine|3,4-methylenedioxymethamphetamine]]<ref name=":0" />
*  [[Norepinephrine reuptake inhibitor|NRI]]
** [[atomoxetine]]<ref name=Flockhart/><ref name="Dean 2020 d887">{{cite book |  vauthors = Dean L | chapter = Atomoxetine Therapy and CYP2D6 Genotype | veditors = Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ | title = Medical Genetics Summaries [Internet]. | location = Bethesda (MD) | publisher=National Center for Biotechnology Information (US) | date=2020-06-29 | pmid=28520366 | url=https://www.ncbi.nlm.nih.gov/books/NBK315951/ | access-date=2024-04-24}}</ref><ref name="Brown Abdel-Rahman van Haandel Gaedigk 2016 pp. 642–650">{{cite journal | vauthors = Brown JT, Abdel-Rahman SM, van Haandel L, Gaedigk A, Lin YS, Leeder JS | title = Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD | journal = Clinical Pharmacology and Therapeutics | volume = 99 | issue = 6 | pages = 642–650 | date = June 2016 | pmid = 26660002 | pmc = 4862932 | doi = 10.1002/cpt.319 }}</ref>
* [[H3 receptor antagonist]]/inverse agonist
** [[pitolisant]]<ref name="Wakix Prescribing Information">{{cite web| title=Wakix pitolisant tablets Prescribing Information| website=Wakix HCP| url=https://www.wakixhcp.com/assets/pdf/WAKIX__pitolisant__tablets_PI_Dec_2022.pdf#page10| access-date=11 January 2023| archive-date=11 January 2023| archive-url=https://web.archive.org/web/20230111213055/https://www.wakixhcp.com/assets/pdf/WAKIX__pitolisant__tablets_PI_Dec_2022.pdf#page10| url-status=live}}</ref>
* [[chlorphenamine]]<ref name=Flockhart/> ([[antihistamine]])
* [[dexfenfluramine]]<ref name=Flockhart/> ([[serotonin]]ergic [[anorectic]])
* [[dextromethorphan]]<ref name=Flockhart/> [[bioactivation|↑]] [into [[dextrorphan]]] ([[antitussive]])
* [[metoclopramide]]<ref name=Flockhart/> ([[dopamine antagonist]])
* [[perhexiline]]<ref name=Flockhart/> ([[antianginal agent]])
* [[phenacetin]]<ref name=Flockhart/> ([[analgesic]])
* [[promethazine]]<ref name=Flockhart/> ([[antihistamine]] [[antiemetic]])
* [[m-tyramine|''m''-tyramine]]<ref name="CYP2D6 tyramine-dopamine metabolism" />
* [[p-tyramine|''p''-tyramine]]<ref name="CYP2D6 tyramine-dopamine metabolism" />
* [[Lysergic acid diethylamide]] (LSD)<ref>{{cite journal | vauthors = Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME | title = Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 10851 | date = May 2021 | pmid = 34035391 | pmc = 8149637 | doi = 10.1038/s41598-021-90343-y | bibcode = 2021NatSR..1110851V }}</ref>
* [[5-MeO-DMT|5-methoxy-N,N-dimethyltryptamine]]<ref>{{cite journal | vauthors = Shen HW, Jiang XL, Winter JC, Yu AM | title = Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions | journal = Current Drug Metabolism | volume = 11 | issue = 8 | pages = 659–666 | date = October 2010 | pmid = 20942780 | pmc = 3028383 | doi = 10.2174/138920010794233495 }}</ref>
* [[Calcium channel blocker]]
** [[diltiazem]] (minor/moderate sensitive substrate) <ref name="DailyMed 2017">{{cite web | title=DILTIAZEM HCL CD- diltiazem hydrochloride capsule, coated, extended release | website=DailyMed | date=1 February 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e39be50-ea17-4077-a2dc-668267049f6a | access-date=31 January 2019 | archive-date=31 January 2019 | archive-url=https://web.archive.org/web/20190131145508/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e39be50-ea17-4077-a2dc-668267049f6a | url-status=live }}</ref>
** [[nifedipine]] (minor/moderate sensitive substrate)<ref name="DailyMed 2012">{{cite web | title=NIFEDIPINE EXTENDED RELEASE- nifedipine tablet, extended release | website=DailyMed | date=29 November 2012 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4617417a-08df-4417-a944-dfc30de183db | access-date=1 February 2019 | archive-date=31 January 2022 | archive-url=https://web.archive.org/web/20220131061535/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4617417a-08df-4417-a944-dfc30de183db | url-status=live }}</ref>
||

'''Strong'''<!--inhibitors-->
* Certain [[Selective serotonin reuptake inhibitor|SSRI]]s
** [[fluoxetine]]<ref name=Flockhart/><ref name=FASS>{{cite web | publisher = [[FASS (drug formulary)]] | title = Kombinera läkemedel| url = http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 | work = Swedish environmental classification of pharmaceuticals | archive-url = https://web.archive.org/web/20020611044953/http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 | archive-date=11 June 2002 }} Facts for prescribers (Fakta för förskrivare), retrieved July 2011</ref>
** [[paroxetine]]<ref name=Flockhart/><ref name=FASS/>
* [[bupropion]]<ref name=Flockhart/><ref name="pmid15876900">{{cite journal | vauthors = Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE | title = Inhibition of CYP2D6 activity by bupropion | journal = Journal of Clinical Psychopharmacology | volume = 25 | issue = 3 | pages = 226–229 | date = June 2005 | pmid = 15876900 | doi = 10.1097/01.jcp.0000162805.46453.e3 | s2cid = 24591644 }}</ref> (non-SSRI antidepressant)
* [[quinidine]]<ref name=Flockhart/><ref name=FASS/> ([[class I antiarrhythmic agent]])
* [[quinine]]<ref>{{cite journal | vauthors = Fasinu PS, Tekwani BL, Avula B, Chaurasiya ND, Nanayakkara NP, Wang YH, Khan IA, Walker LA | title = Pathway-specific inhibition of primaquine metabolism by chloroquine/quinine | journal = Malaria Journal | volume = 15 | issue = 1 | pages = 466 | date = September 2016 | pmid = 27618912 | pmc = 5020452 | doi = 10.1186/s12936-016-1509-x | doi-access = free }}</ref>
* [[cinacalcet]]<ref name=Flockhart/> ([[calcimimetic]])
* [[ritonavir]]<ref name=FASS/> ([[antiretroviral]])
* [[cannabidiol]]<ref>{{cite web|url=https://doh.dc.gov/sites/default/files/dc/sites/doh/publication/attachments/Medical%20Cannabis%20Adverse%20Effects%20and%20Drug%20Interactions_0.pdf|title=Medical Cannabis Adverse Effects & Drug Interactions|access-date=28 October 2019|archive-date=14 December 2019|archive-url=https://web.archive.org/web/20191214100618/https://doh.dc.gov/sites/default/files/dc/sites/doh/publication/attachments/Medical%20Cannabis%20Adverse%20Effects%20and%20Drug%20Interactions_0.pdf|url-status=live}}</ref>

'''Moderate'''<!--inhibitors-->
* [[duloxetine]]<ref name=Flockhart/> ([[serotonin-norepinephrine reuptake inhibitor|SNRI]])
* [[terbinafine]]<ref name=Flockhart/> ([[Antifungal medication|antifungal]])

'''Weak'''<!--inhibitors-->
* [[amiodarone]]<ref name=Flockhart>{{cite web |title=Drug Interactions: Cytochrome P<sub>450</sub> Drug Interaction Table |publisher=[[Indiana University School of Medicine]] |year=2007 |url=http://medicine.iupui.edu/flockhart/table.htm |access-date=25 July 2010 |archive-date=10 October 2007 |archive-url=https://web.archive.org/web/20071010053126/http://medicine.iupui.edu/flockhart/table.htm |url-status=live }} Retrieved in July 2011</ref> ([[antiarrhythmic]])
* [[berberine]]<ref>{{cite journal | vauthors = Zhao Y, Hellum BH, Liang A, Nilsen OG | title = Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs | journal = Phytotherapy Research | volume = 29 | issue = 6 | pages = 825–834 | date = June 2015 | pmid = 25640685 | doi = 10.1002/ptr.5285 | s2cid = 24002845 }}</ref><ref name="pmid22855269">{{cite journal | vauthors = Hermann R, von Richter O | title = Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions | journal = Planta Medica | volume = 78 | issue = 13 | pages = 1458–1477 | date = September 2012 | pmid = 22855269 | doi = 10.1055/s-0032-1315117 | doi-access = free }}</ref><ref name="pmid30086269">{{cite journal | vauthors = Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, Xu X, Fang Q, Liang Z, Li B | title = The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins | journal = Chemico-Biological Interactions | volume = 293 | issue =  | pages = 115–123 | date = September 2018 | pmid = 30086269 | doi = 10.1016/j.cbi.2018.07.022 | s2cid = 206489481 | bibcode = 2018CBI...293..115F }}</ref> (an [[alkaloid]] found in plants like [[berberis]])
* [[buprenorphine]]<ref name="pmid12756210">{{cite journal | vauthors = Zhang W, Ramamoorthy Y, Tyndale RF, Sellers EM | title = Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro | journal = Drug Metabolism and Disposition | volume = 31 | issue = 6 | pages = 768–772 | date = June 2003 | pmid = 12756210 | doi = 10.1124/dmd.31.6.768 }}</ref> (in opioid addiction)
* [[cimetidine]]<ref name=Flockhart/> ([[H2-receptor antagonist]])
* [[citalopram]]<ref name=Flockhart/><ref name = "drugs.com">{{cite web| url = https://www.drugs.com/pro/citalopram-oral-solution.html| title = Citalopram Oral Solution| work = Drugs.com| access-date = 23 January 2018| archive-date = 8 February 2018| archive-url = https://web.archive.org/web/20180208171338/https://www.drugs.com/pro/citalopram-oral-solution.html| url-status = live}}</ref> ([[Selective serotonin reuptake inhibitor|SSRI]])
* [[escitalopram]]<ref name=Flockhart/><ref name = "drugs.com" /><ref name="UpToDate Escitalopram">{{cite web | title=Escitalopram-drug-information | website=UpToDate | url=https://www.uptodate.com/contents/escitalopram-drug-information | access-date=22 May 2019 | archive-date=28 October 2020 | archive-url=https://web.archive.org/web/20201028173743/https://www.uptodate.com/contents/escitalopram-drug-information | url-status=live }}</ref> ([[Selective serotonin reuptake inhibitor|SSRI]])
* [[fluvoxamine]]<ref name="FDA_drug_development">{{cite journal|title=Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers|journal=FDA|date=26 May 2021|url=https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers|access-date=21 June 2020|archive-date=4 November 2020|archive-url=https://web.archive.org/web/20201104173036/https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers|url-status=live}}</ref>  ([[Selective serotonin reuptake inhibitor|SSRI]])
* [[methylphenidate]]<ref>{{cite journal | url = http://www.gjpsy.uni-goettingen.de/gjp-article-nevels.pdf | title = Methylphenidate and Its Under-recognized, Under- explained, and Serious Drug Interactions: A Review of the Literature with Heightened Concerns | journal = German Journal of Psychiatry | date = July 2013 | pages = 29–42 | vauthors = Nevels RM, Weiss NH, Killebrew AE, Gontkovsky ST | access-date = 31 August 2016 | archive-date = 9 April 2018 | archive-url = https://web.archive.org/web/20180409223309/http://www.gjpsy.uni-goettingen.de/gjp-article-nevels.pdf | url-status = dead }}</ref>
* [[diltiazem]]<ref name="DailyMed 2017"/>
* [[felodipine]]<ref name="Bailey Bend Arnold Tran 1996 pp. 25–33">{{cite journal | vauthors = Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD | title = Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice | journal = Clinical Pharmacology and Therapeutics | volume = 60 | issue = 1 | pages = 25–33 | date = July 1996 | pmid = 8689808 | doi = 10.1016/s0009-9236(96)90163-0 | s2cid = 1246705 }}</ref><ref name="Lown Bailey Fontana Janardan pp. 2545–2553">{{cite journal | vauthors = Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB | title = Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression | journal = The Journal of Clinical Investigation | volume = 99 | issue = 10 | pages = 2545–2553 | date = May 1997 | pmid = 9153299 | pmc = 508096 | doi = 10.1172/jci119439 }}</ref><ref name="Guengerich Brian Iwasaki Sari 1991 pp. 1838–44">{{cite journal | vauthors = Guengerich FP, Brian WR, Iwasaki M, Sari MA, Bäärnhielm C, Berntsson P | title = Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4 | journal = Journal of Medicinal Chemistry | volume = 34 | issue = 6 | pages = 1838–1844 | date = June 1991 | pmid = 2061924 | doi = 10.1021/jm00110a012 }}</ref>
* [[mirtazapine]]<ref>{{cite journal | vauthors = Owen JR, Nemeroff CB | title = New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine | journal = Depression and Anxiety | volume = 7 | issue = Suppl 1 | pages = 24–32 | date = 30 May 1998 | pmid = 9597349 | doi = 10.1002/(SICI)1520-6394(1998)7:1+<24::AID-DA7>3.0.CO;2-F | url = https://researchers.dellmed.utexas.edu/en/publications/new-antidepressants-and-the-cytochrome-psub450sub-system-focus-on | access-date = 1 November 2019 | url-status = dead | s2cid = 34832618 | url-access = subscription | archive-url = https://web.archive.org/web/20191101160947/https://researchers.dellmed.utexas.edu/en/publications/new-antidepressants-and-the-cytochrome-psub450sub-system-focus-on | archive-date = 1 November 2019 }}</ref>
* [[sertraline]]<ref name="FDA_drug_development" /><ref name="pmid15257068">{{cite journal | vauthors = Spina E, D'Arrigo C, Migliardi G, Morgante L, Zoccali R, Ancione M, Madia A | title = Plasma risperidone concentrations during combined treatment with sertraline | journal = Therapeutic Drug Monitoring | volume = 26 | issue = 4 | pages = 386–390 | date = August 2004 | pmid = 15257068 | pmc =  | doi = 10.1097/00007691-200408000-00008 }}</ref><ref name="pmid10950472">{{cite journal | vauthors = Sproule BA, Otton SV, Cheung SW, Zhong XH, Romach MK, Sellers EM | title = CYP2D6 inhibition in patients treated with sertraline | journal = Journal of Clinical Psychopharmacology | volume = 17 | issue = 2 | pages = 102–106 | date = April 1997 | pmid = 10950472 | pmc =  | doi = 10.1097/00004714-199704000-00007 }}</ref> ([[Selective serotonin reuptake inhibitor|SSRI]])

'''<!--inhibitors of-->Unspecified potency'''
* [[antipsychotic]]s
** [[haloperidol]]<ref name=fass-codeine>{{cite web | publisher = [[FASS (drug formulary)|FASS]] | url = http://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=19731109000032&DocTypeID=6 | work = The Swedish official drug catalog | title = Kodein Recip | archive-url = https://web.archive.org/web/20110719114446/http://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=19731109000032&DocTypeID=6 | archive-date=19 July 2011 }} Last reviewed 8 April 2008</ref><ref name=Flockhart/><ref name="pmid11167668">{{cite journal | vauthors = Shin JG, Kane K, Flockhart DA | title = Potent inhibition of CYP2D6 by haloperidol metabolites: stereoselective inhibition by reduced haloperidol | journal = British Journal of Clinical Pharmacology | volume = 51 | issue = 1 | pages = 45–52 | date = January 2001 | pmid = 11167668 | pmc = 2014431 | doi = 10.1046/j.1365-2125.2001.01313.x }}</ref> 
** [[perphenazine]]<ref name=Flockhart/><ref name=fass-codeine/>
** [[thioridazine]]<ref name=fass-codeine/>
** [[zuclopenthixol]]<ref name=fass-codeine/>
** [[chlorpromazine]]<ref name=Flockhart/>
* [[antihistamine]]s ([[H1-receptor antagonists]])
** [[promethazine]]<ref name="pmid11936702">{{cite journal | vauthors = He N, Zhang WQ, Shockley D, Edeki T | title = Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes | journal = European Journal of Clinical Pharmacology | volume = 57 | issue = 12 | pages = 847–851 | date = February 2002 | pmid = 11936702 | doi = 10.1007/s00228-001-0399-0 | s2cid = 601644 }}</ref> ([[sedative|antipsychotic]])
** [[chlorphenamine]]<ref name=Flockhart/>
** [[diphenhydramine]]<ref name=Flockhart/>
** [[hydroxyzine]]<ref name=Flockhart/>
** [[tripelennamine]]<ref name=Flockhart/>
* [[celecoxib]]<ref name=Flockhart/> ([[NSAID]])
* [[clemastine]]<ref name=Flockhart/> ([[antihistamine]] and [[anticholinergic]])
* [[clomipramine]]<ref name=Flockhart/> ([[tricyclic antidepressant]])
* [[cocaine]]<ref name=Flockhart/> ([[stimulant]])
* [[doxepin]]<ref name=Flockhart/> ([[tricyclic antidepressant]], [[anxiolytic]])
* [[doxorubicin]]<ref name=Flockhart/> ([[chemotherapeutic]])
* [[halofantrine]]<ref name=Flockhart/> (in [[malaria]])
* [[hyperforin]] ([[St. Johns Wort]])<ref>{{cite journal |doi=10.1080/13880200490512034 |title=''In Vitro'' Activity of St. John's Wort Against Cytochrome P450 Isozymes and P-Glycoprotein |journal=Pharmaceutical Biology |volume=42 |issue=2 |pages=159–69 |year=2008 | vauthors = Foster BC, Sockovie ER, Vandenhoek S, Bellefeuille N, Drouin CE, Krantis A, Budzinski JW, Livesey J, Arnason JR |s2cid=2366709 }}</ref>
* [[levomepromazine]]<ref name=Flockhart/> ([[antipsychotic]])
* [[methadone]]<ref name=Flockhart/> ([[opioid]] and [[anti-addictive]])
* [[metoclopramide]]<ref name=Flockhart/> ([[antiemetic]], [[prokinetic]])
* [[mibefradil]]<ref name=Flockhart/> ([[calcium channel blocker]])
* [[midodrine]]<ref name=Flockhart/> ([[Alpha-1 adrenergic agonist|α<sub>1</sub> agonist]])
* [[moclobemide]]<ref name=Flockhart/> ([[antidepressant]])
* [[Niacin (nutrient)|niacin]]<ref name = "Gaudineau_2004">{{cite journal | vauthors = Gaudineau C, Auclair K | title = Inhibition of human P450 enzymes by nicotinic acid and nicotinamide | journal = Biochemical and Biophysical Research Communications | volume = 317 | issue = 3 | pages = 950–956 | date = May 2004 | pmid = 15081432 | doi = 10.1016/j.bbrc.2004.03.137 | author-link2 = Karine Auclair }}</ref> ([[nicotinic acid]]) and its form – [[niacinamide]] ([[nicotinamide]]), collectively called as [[vitamin B3]]
* [[sesame]]<ref name="pmid30558213">{{cite journal | vauthors = Briguglio M, Hrelia S, Malaguti M, Serpe L, Canaparo R, Dell'Osso B, Galentino R, De Michele S, Dina CZ, Porta M, Banfi G | title = Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic/Pharmacodynamic Profiles | journal = Pharmaceutics | volume = 10 | issue = 4 | pages = 277 | date = December 2018 | pmid = 30558213 | pmc = 6321138 | doi = 10.3390/pharmaceutics10040277 | doi-access = free }}</ref> (seeds, oil)
* [[ticlopidine]]<ref name=Flockhart/> ([[antiplatelet drug|antiplatelet]])

||

'''Strong'''<!--inducers-->
* [[glutethimide]]<!-- <ref name=Dave/> --> ([[hypnotic|hypnotic sedative]])
'''<!--inducers of-->Unspecified potency'''
* [[haloperidol]]<ref>{{cite journal | vauthors = Kudo S, Ishizaki T | title = Pharmacokinetics of haloperidol: an update | journal = Clinical Pharmacokinetics | volume = 37 | issue = 6 | pages = 435–456 | date = December 1999 | pmid = 10628896 | doi = 10.2165/00003088-199937060-00001 | s2cid = 71360020 }}</ref> ([[typical antipsychotic]])
|-
|}

===Dopamine biosynthesis===
{{Catecholamine and trace amine biosynthesis|caption=In humans, [[catecholamine]]s and phenethylaminergic [[trace amine]]s 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.<ref name="CYP2D6 tyramine-dopamine metabolism" /> Similarly, CYP2D6 also metabolizes [[m-tyramine|''m''-tyramine]] into dopamine.<ref name="CYP2D6 tyramine-dopamine metabolism" />}}

== References ==
{{reflist|colwidth=35em}}

== Further reading ==
{{refbegin|colwidth=35em}}
* {{cite journal | vauthors = Smith G, Stubbins MJ, Harries LW, Wolf CR | title = Molecular genetics of the human cytochrome P450 monooxygenase superfamily | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 28 | issue = 12 | pages = 1129–1165 | date = December 1998 | pmid = 9890157 | doi = 10.1080/004982598238868 }}
* {{cite journal | vauthors = Wolf CR, Smith G | title = Cytochrome P450 CYP2D6 | journal = IARC Scientific Publications | issue = 148 | pages = 209–229 | year = 1999 | pmid = 10493260 }}
* {{cite journal | vauthors = Ding X, Kaminsky LS | title = Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts | journal = Annual Review of Pharmacology and Toxicology | volume = 43 | pages = 149–173 | year = 2003 | pmid = 12171978 | doi = 10.1146/annurev.pharmtox.43.100901.140251 }}
* {{cite journal | vauthors = Lilienfeld S | title = Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease | journal = CNS Drug Reviews | volume = 8 | issue = 2 | pages = 159–176 | year = 2006 | pmid = 12177686 | pmc = 6741688 | doi = 10.1111/j.1527-3458.2002.tb00221.x }}
* {{cite journal | vauthors = Yu AM, Idle JR, Gonzalez FJ | title = Polymorphic cytochrome P450 2D6: humanized mouse model and endogenous substrates | journal = Drug Metabolism Reviews | volume = 36 | issue = 2 | pages = 243–277 | date = May 2004 | pmid = 15237854 | doi = 10.1081/DMR-120034000 | url = https://zenodo.org/record/1236072 | access-date = 5 July 2019 | url-status = live | s2cid = 11330784 | archive-url = https://web.archive.org/web/20220629150042/https://zenodo.org/record/1236072 | archive-date = 29 June 2022 }}
* {{cite journal | vauthors = Abraham JE, Maranian MJ, Driver KE, Platte R, Kalmyrzaev B, Baynes C, Luccarini C, Shah M, Ingle S, Greenberg D, Earl HM, Dunning AM, Pharoah PD, Caldas C | title = CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen | journal = Breast Cancer Research | volume = 12 | issue = 4 | pages = R64 | year = 2010 | pmid = 20731819 | pmc = 2949659 | doi = 10.1186/bcr2629 | doi-access = free }}
* {{cite journal | vauthors = Abraham JE, Maranian MJ, Driver KE, Platte R, Kalmyrzaev B, Baynes C, Luccarini C, Earl HM, Dunning AM, Pharoah PD, Caldas C | title = CYP2D6 gene variants and their association with breast cancer susceptibility | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 20 | issue = 6 | pages = 1255–1258 | date = June 2011 | pmid = 21527579 | doi = 10.1158/1055-9965.EPI-11-0321 | s2cid = 32846974 | doi-access =  }}
{{refend}}

== External links ==
* [http://medicine.iupui.edu/flockhart/2D6.htm#2D6sub Flockhart Lab Cyp2D6 Substrates Page] at [[Indiana University-Purdue University Indianapolis|IUPUI]]
* [https://web.archive.org/web/20081207081045/http://www.pharmgkb.org/search/annotatedGene/cyp2d6/index.jsp PharmGKB: Annotated PGx Gene Information for CYP2D6]
* [https://www.pharmvar.org/gene/CYP2D6 Pharmvar Gene:CYP2D6]
* {{UCSC gene info|CYP2D6}}
* {{PDBe-KB2|P10635|Cytochrome P450 2D6}}

{{PDB Gallery|geneid=1565}}
{{Cytochrome P450}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

[[Category:Cytochrome P450|2]]
[[Category:EC 1.14.14]]
[[Category:Amphetamine]]
[[Category:Pharmacogenomics]]