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cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

Function: 1) responsible for the metabolism of many drugs & environmental chemicals 2) metabolism of codeine, dihydrocodeine, hydrocodone & tramadol by cyt P450 2D6 are necessary for conversion to an active analgesic metabolite 3) inducers - not inducible 4) inhibitors - amiodarone - asenapine - bupropion - celecoxib - chloramphenicol - chloroquine - chlorpheniramine - cimetidine - cinacalcet - citalopram - clemastine - clomipramine - cocaine - darifenacin - darunavir - desipramine - diphenhydramine - doxepin - doxorubicin - dronedarone - duloxetine - escitalopram - everolimus - fluoxetine - fluphenazine - fluvoxamine - halofantrine - haloperidol - hydroxychloroquine - iloperidone - imatinib - methadone - nicardipine - paroxetine - perphenazine - Piper methysticum (Kava-kava) - pomegranate - propafenone - propoxyphene - propranolol - quinacrine - quinidine - quinine - ranitidine - ranolazine - ritonavir - rolapitant - sertraline - terbinafine - thioridazine - ticlopidine - tipranavir - tripelennamine 5) substrates - amitriptyline - amphetamine - asenapine - atomoxetine - bisoprolol - carvedilol - cevimeline - chlorpromazine - chlorpropamide - ciclesonide - cinacalcet - clomipramine - clozapine - codeine - cyclobenzaprine - darifenacin - desipramine - dexfenfluramine - dextromethorphan - dolasetron - donepezil - doxepin - duloxetine - encainide - fenfluramine - fentanyl - fesoterodine - flecainide - fluoxetine - fluphenazine - fluvoxamine - formoterol - galantamine - haloperidol - hydrocodone - iloperidone - imipramine - lidocaine - maprotiline - meperidine - methadone - methamphetamine - metoprolol - mexiletine - mirtazapine - morphine - nebivolol - nortriptyline - olanzapine - ondansetron - oxycodone - paroxetine - perphenazine - pindolol - propafenone - propoxyphene - propranolol - quetiapine - ranolazine - risperidone - ritonavir - tamoxifen - tetrabenazine - thioridazine - timolol - tolterodine - tramadol - trazodone - venlafaxine Compartment: membrane-bound, endoplasmic reticulum Expression: - induced by pregnancy - not inducible [10] Inhibition: - quinidine & ritonavir are potent inhibitors of cyt P450 2D6 Polymorphism: - highly polymorphic - 7% of Caucasians & 2% of Asians have reduced cyt P450 2D6 activity (poor metabolizers of cyt P450 2D6-metabolized drugs) [6] - allele CYP2D6*7 was also known as CYP2D6E allele CYP2D6*9 as CYP2D6C allele CYP2D6*10 as CYP2D6J allele CYP2D6*17 as CYP2D6Z Laboratory: - CYP2D6 enzyme activity - CYP2D6 genotyping - CYP2D6 gene deletion - CYP2D6 gene mutation

Related

CYP2D6 gene mutation CYP2D6 genotyping cyt P450 2D6 gene

General

cytochrome P450

Properties

SIZE: MW = 56 kD entity length = 497 aa COMPARTMENT: endoplasmic reticulum MOTIF: Iron [Fe]-binding site SITE: 443-443 SUBSTRATE: amitriptyline amphetamine asenapine atomoxetine bisoprolol carvedilol cevimeline chlorpromazine chlorpropamide ciclesonide cinacalcet clomipramine clozapine codeine cyclobenzaprine darifenacin desipramine dexfenfluramine dextromethorphan dolasetron donepezil doxepin duloxetine encainide fenfluramine fentanyl fesoterodine flecainide fluoxetine fluphenazine fluvoxamine formoterol galantamine haloperidol hydrocodone iloperidone imipramine lidocaine maprotiline meperidine methadone methamphetamine metoprolol mexiletine mirtazapine morphine nebivolol (Bystolic) nortriptyline olanzapine ondansetron oxycodone paroxetine perphenazine pindolol propafenone propoxyphene propranolol quetiapine ranolazine risperidone ritonavir tamoxifen tetrabenazine thioridazine timolol tolterodine tramadol trazodone venlafaxine INHIBITORS: amiodarone asenapine bupropion celecoxib chloramphenicol chloroquine chlorpheniramine cimetidine cinacalcet citalopram clemastine clomipramine cocaine darifenacin darunavir desipramine diphenhydramine doxepin doxorubicin dronedarone duloxetine escitalopram everolimus fluoxetine fluphenazine fluvoxamine halofantrine haloperidol hydroxychloroquine iloperidone imatinib methadone moclobemide nicardipine nilotinib paroxetine pazopanib perphenazine Piper methysticum (Kava-Kava) pomegranate propafenone propoxyphene propranolol quinacrine quinidine quinine ranitidine ranolazine ritonavir rolapitant sertraline terbinafine thioridazine ticlopidine tipranavir tripelennamine

Database Correlations

OMIM correlations UniProt P10635 Pfam PF00067 Entrez Gene 1565 ENZYME 1.14.14.1

References

  1. OMIM :accession 124030
  2. UniProt :accession P10635
  3. Tarascon Pharmacopoeia, 2001
  4. Pirmohamed M & Park BK, Toxicology 192:23-32, 2003
  5. Prescriber's Letter 11(4):24 2004
  6. http://pi.lilly.com/us/strattera-pi.pdf
  7. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  8. Cytochrome P450 Allele Nomenclature committee, CYP2D6 alleles http://www.cypalleles.ki.se/cyp2d6.htm
  9. Wikipedia, CYP2D6 entry http://en.wikipedia.org/wiki/CYP2D6
  10. Prescriber's Letter 17(1): 2010 Cytochrome P450 Drug Interactions CHART: Cytochrome P450 Drug Interactions COMMENTARY: Proton Pump Inhibitor and Plavix Interaction: An Update Detail-Document#: 260112 (subscription needed) http://www.prescribersletter.com
  11. Prescriber's Letter 18(3): 2011 CHART: Cytochrome P450 Drug Interactions Detail-Document#: 270307 (subscription needed) http://www.prescribersletter.com