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Topic: CYP2D6

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	CYP2D6 - cytochrome P450, family 2, subfamily D, polypeptide 6
		Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis.
		CYP2D6 is the major target autoantigen of LKM-1 and expressed on plasma membrane (PM) of hepatocytes, suggesting a pathogenic role for anti-LKM-1 in liver injury as a trigger.
		CYP2D6, Cyp2d-9 and both mutant CYP2D6 proteins were co-expressed with NADPH cytochrome P-450 reductase as a functional mono-oxygenase system in Escherichia coli and their relative catalytic activities towards bufuralol and testosterone were determined.
	www.ihop-net.org /UniPub/iHOP/gg/87584.html (5552 words)

	Erowid MDMA Vault : Pharmacology : CYP2D6 Metabolism Issues for MDMA (CYP-2D6)
		CYP2D6 metabolizes MDMA into DHMA (dihydroxy-methamphetamine) and it is still possible that poor metabolizers would have decreased formation of DHMA compared to strong CYP2D6 metabolizers.
		The human debrisoquine 4-hydroxylase (CYP2D6) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene.
		The hyperthermic and neurotoxic effects of 'Ecstasy' (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype, Br J Pharmacol, 1995; 115(7):1281-9.
	www.erowid.org /chemicals/mdma/mdma_pharmacology1.shtml (1158 words)

	CYP2D6 - Wikipedia, the free encyclopedia
		Cytochrome P450 2D6 (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.
		Whilst CYP2D6 is involved in the oxidation of a wide range of substrates of all the CYPs, there is considerable variability in its expression in the liver.
		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).
	en.wikipedia.org /wiki/CYP2D6 (545 words)

	Contribution of Polymorphisms in UDP-Glucuronosyltransferase and CYP2D6 to the Individual Variation in Disposition of ...
		CYP2D6 strongly affect the pharmacokinetics and disposition of carvedilol in Japanese.
		CYP2D6 is responsible for the formation of 4’-hydroxy carvedilol and 5’-hydroxy carvedilol, and both metabolites are excreted into urine (6.4%) [7].
		Therefore, we should not disregard the influence of CYP2D6 in discussing the disposition of carvedilol, although glucuronidation is the major metabolic pathway of carvedilol in humans.
	www.ualberta.ca /~csps/JPPS9(1)/Takekuma,Y/carvedilol.htm (1416 words)

	Health and DNA: 2D6
		CYP2D6 is responsible for activating the pro-drugs codeine and other opioids into their active forms.
		Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic liver enzyme of the cytochrome P450 super family involved with the metabolism and elimination of many commonly prescribed drugs.
		CYP2D6 activity does not appear to change with age; however, CYP2D6 activity may appear to be altered because of age-associated changes in hepatic blood flow or a decrease in renal elimination of metabolites.
	www.healthanddna.com /professional/2D6testmenu.htm (2215 words)

	Environmental Genome Project Research Activities - Functional Effects of Allelic Variation in Human CYP2D6
		The long term aim of the present proposal is to understand the role of human cytochrome P-450 2D6 in the protection from, or predisposition to neurological disease.
		CYP2D6 is polymorphically expressed in human liver, lung and brain, with over 17 distinct alleles described in the literature, eight of which encode for non-null variants.
		CYP2D6 plays a key role in the metabolism of many important psychoactive drugs, such as the activation of codeine to morphine, and is known to detoxify MPTP, a thermal breakdown product of 'street heroin' which causes Parkinsonian symptoms in susceptible individuals.
	www.niehs.nih.gov /envgenom/abstract/r01-9894.htm (326 words)

	Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the U.S. Population: Clinical Implications -- Bernard et ...
		Genetic polymorphism of CYP2D6 in Karnataka and Andhra Pradesh population in India.
		Genetic analysis of the CYP2D6 locus in a Hong Kong Chinese population.
		CYP2D6 extensive, intermediate and poor phenotypes and genotypes in a Polish population.
	theoncologist.alphamedpress.org /cgi/content/full/11/2/126 (4625 words)

	EHS: Mosby's Drug Consult - Drug Updates - Atomoxetine Hydrochloride 003578 (Site not responding. Last check: 2007-11-02)
		Coadministration of atomoxetine HCl with potent inhibitors of CYP2D6, such as fluoxetine, paroxetine, or quinidine, results in a substantial increase in atomoxetine plasma exposure, and dosing adjustment may be necessary (see Drug-Drug Interactions).
		Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine.
		CYP2D6 Metabolism: Poor metabolizers (PMs) of CYP2D6 have a 10-fold higher AUC and a 5-fold higher peak concentration to a given dose of atomoxetine HCl compared with extensive metabolizers (EMs).
	www.mosbysdrugconsult.com /DrugConsult/003578.html (6303 words)

	Authors: H
		We designed a case control study nested within a prospective population-based cohort study in which cases and controls were sampled from the same source population.
		To assess the significance of the CYP2D6 gene in PD, we investigated two mutant alleles, CYP2D63 and CYP2D64, associated with poor metabolism and the wild type allele in 80 patients with PD and 156 matched controls, frequency matched on age and gender.
		This study demonstrates that regulation of D(1) receptor expression in the brain of patients dying with Parkinson's disease that were treated with L-DOPA is confined to small alterations in restricted brain regions.
	lansbury.bwh.harvard.edu /Literature/authors_h.htm (2243 words)

	Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels
		CYP2D6 PM and EM Variants and drug exposure and risk- “population, who are known to have a genetic defect leading to reduced levels of activity of P450 2D6.
		CYP2D6 is thought to be the major enzyme in the 4’- and 5’-hydroxylation of carvedilol, with a potential contribution from 3A4.
		Because the difference decreases at high doses and is mitigated by the lack of the active 5-hydroxy metabolite in the slow metabolizers, and because steady-state conditions are achieved after four to five days of dosing in all patients, the recommended dosing regimen of RYTHMOL SR is the same for all patients.
	www.fda.gov /cder/genomics/genomic_biomarkers_table.htm (4381 words)

	Psycoloquy 12(005): A Role for Cyp2d6 in Nicotine Metabolism?
		CYP2D6 may have an important constitutive function in neurotransmitter metabolism and CYP2D6 genotype is thought to be a critical determinant in the success of antidepressant drug treatment.
		This was further confirmed by the observation that the CYP2D6 phenotype of an individual known to be deficient in nicotine C-oxidation was that of an extensive metaboliser (Benowitz et al.
		CYP2D6 in vitro activity is competitively inhibited by serotonin, tryptamine and dopamine, and noncompetitively inhibited by adrenaline and noradrenaline (Martinez et al.
	www.cogsci.ecs.soton.ac.uk /cgi/psyc/newpsy?12.005 (3221 words)

	Single-Step Assays to Analyze CYP2D6 Gene Polymorphisms in Asians: Allele Frequencies and a Novel *14B Allele in ...
		CYP2D6 allele sequences (29), and assignment of the alleles
		Polymorphisms in CYP2D6 duplication-negative individuals with the ultrarapid metabolizer phenotype: a role for the CYP2D6*35 allele in ultrarapid metabolism?.
		Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population.
	www.clinchem.org /cgi/content/full/48/7/983 (3694 words)

	Cytochrome P450: New Nomenclature and Clinical Implications
		CYP2D6 is responsible for the metabolism of many psychotherapeutic agents.
		CYP2D6 has been studied extensively because it exhibits genetic polymorphism, meaning that distinct population differences are apparent in its expression or activity.
		Poor metabolizers of CYP2D6 substrates are at risk for postural hypotension and antipsychotic side effects such as oversedation, because several antipsychotic agents are metabolized by CYP2D6.
	www.aafp.org /afp/980101ap/cupp.html (4175 words)

	Mechanism-Based Inactivation of CYP2D6 by 5-Fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyrimidine -- ...
		Inactivation of CYP2D6 in HL microsomes by SCH 66712.
		of a catalytic step(s) in the inactivation of CYP2D6.
		SCH 66712 is a potent mechanism-based inactivator of CYP2D6.
	dmd.aspetjournals.org /cgi/content/full/29/6/863 (2873 words)

	Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte plasma membrane -- Muratori et al. 46 (4): 553 -- ...
		AIH and HCV related LKM1 recognise CYP2D6 exposed on the plasma membrane of isolated hepatocytes.
		The breakdown of the immunological tolerance to CYP2D6 is the
		A new approach to cytochrome CYP2D6 antibody detection in autoimmune hepatitis type-2 (AIH-2) and chronic hepatitis C virus (HCV) infection: a sensitive and quantitative radioligand assay.
	gut.bmj.com /cgi/content/full/46/4/553 (4866 words)

	Genetic Testing - CYP2D6 (Site not responding. Last check: 2007-11-02)
		When Eli Lilly states in the PDR regarding Strattera, "has a half life of about 5 hours." If you are a poor metabolizer, Lilly states, "plasma half life of about 24 hours." If a person were to use the recommended dosage of Strattera and be a poor metabolizer, the toxic buildup would be astounding.
		35% of the population have a non-functional CYP2D6.
		35% of the population > have a non-functional CYP2D6.
	www.rxlist.com /rxboard/ultram.pl?noframes;read=2624 (1727 words)

	Contribution of Hepatocyte Nuclear Factor-4 to Down-Regulation of CYP2D6 Gene Expression by Nitric Oxide -- Hara and ...
		CYP2D6 is expressed in the liver, intestine, and kidney, where it mediates the oxidative metabolism of such clinically important
		CYP2D6 is genetically polymorphic, and the prevalence of poor-metabolizers,
		80 and +65 of the CYP2D6 gene was responsible for the
	molpharm.aspetjournals.org /cgi/content/full/61/1/194 (4915 words)

	The Relative Contribution of Monoamine Oxidase and Cytochrome P450 Isozymes to the Metabolic Deamination of the Trace ...
		Inhibition of tryptophol formation from tryptamine with CYP2D6 substrates, quinidine, and pargyline by human liver microsomes (A) and recombinant human monoamine oxidase-A enzyme (B).
		to the false conclusion that CYP2D6 was responsible for the
		Granvil CP, Krausz KW, Gelboin HV, Idle JR, and Gonzalez FJ (2002) 4-Hydroxylation of debrisoquine by human CYP1A1 and its inhibition by quinidine and quinine.
	jpet.aspetjournals.org /cgi/content/full/304/2/539 (3767 words)

	4-Hydroxylation of Debrisoquine by Human CYP1A1 and Its Inhibition by Quinidine and Quinine -- Granvil et al. 301 (3): ...
		Inhibition of CYP2D6- and CYP1A1-Mediated 4-Hydroxylation of Debrisoquine by Quinine and Quinidine.
		CYP2D6 genotype and extent of debrisoquine 4-hydroxylation in
		Mbanefo C, Bababunmi EA, Mahgoub A, Sloan TP, Idle JR and Smith RL (1980) A study of the debrisoquine hydroxylation polymorphism in a Nigerian population.
	jpet.aspetjournals.org /cgi/content/full/301/3/1025 (5742 words)

	Perhexiline - Wikipedia, the free encyclopedia
		CYP2D6 accounts for only a small percentage of total hepatic CYP450s but it is one of the main pathways for phase one metabolism of xenobiotics.
		It is estimated that 7–10% of Caucasians are CYP2D6 PMs.
		Most PMs have an autosomal recessive polymorphism in the CYP2D6 locus which results in the severely compromised metabolism of at least 25 drugs.
	en.wikipedia.org /wiki/Perhexiline (757 words)

	PubMed CYP2D6 Studies
		Of these two, the CYP2D6 is responsible for metabolizing antidepressants and antipsychotic drugs, amongst others.
		CYP2D6 Deficiency-Related Death In 1995, the FDA reported on the death of a 9-year old boy who at various times had received clonidine, fluoxetine, and methylphenidate, and who was found to have extremely high fluoxetine blood levels.
		This appears to be the first report of toxicity and death in a child with confirmed polymorphism of CYP2D6.
	www.antidepressantsfacts.com /p-450-enzyme-studies.htm (1611 words)

	Dissertations from Karolinska Institutet - Published by Karolinska Institutet Karolinska Institutet - ki.se
		These results suggest the involvement of CYP2D6 in the metabolism of haloperidol at low doses of haloperidol (<20mg daily), while another enzyme, probably CYP3A4, is the most important one at higher doses.
		Although the genotypes can predict the activity of CYP2D6 and CYP2C19, the clinical importance is limited, when the enzyme is saturated at high dose as in the case of haloperidol and when active metabolites are formed as in the case of risperidone.
		Interethnic differences in drug metabolic capacity ought to be considered even when usual doses are used as in the case of omeprazole in Korean patients with acid related disorders.
	diss.kib.ki.se /2002/91-7349-169-1 (779 words)

	Correspondence re: C. Chen et al., CYP2D6 Genotype and the Incidence of Anal and Vulvar Cancer. Cancer Epidemiol. ... (Site not responding. Last check: 2007-11-02)
		Correspondence re: C. Chen et al., CYP2D6 Genotype and the Incidence of Anal and Vulvar Cancer.
		CYP2D6 is an ineffective catalyst of NNK metabolic activation.
		, CYP2D6 genotype and the incidence of anal and vulvar cancer.
	cebp.aacrjournals.org /cgi/content/full/8/9/839 (963 words)

	Effects of G169R and P34S Substitutions Produced by Mutations of CYP2D6*14 on the Functional Properties of CYP2D6 ...
		CYP2D6 is a polymorphic enzyme that catalyzes the oxidation of various drugs.
		wild-type CYP2D6 and mutated CYP2D6 G169R cDNA to a pTARGET Mammalian
		CYP2D6) was approximately one-third (32%) of that of 2D6WT (1.17
	dmd.aspetjournals.org /cgi/content/full/30/11/1201 (3588 words)

	LGC: Business Sectors:Healthcare and Genetics:Services:CYP2D6 Licensing
		The P450 CYP2D6 enzyme metabolises approximately one quarter of all prescribed drugs and is routinely referenced in prescription guidelines due to its high frequency of polymorphic variance.
		In the FDA March 2005 Guidance for Industry Pharmacogenomic Data Submissions, CYP2D6 is particulary noted as an example of a known valid biomarker.
		The most common polymorphisms found in the CYP2D6 gene are the subject of a patent portfolio in the name of ICRF and exclusively licensed to the University of Dundee.
	www.lgc.co.uk /service.asp?intElement=6091 (144 words)

	Nicotine Metabolism and CYP2D6 Phenotype in Smokers -- Caporaso et al. 10 (3): 261 -- Cancer Epidemiology Biomarkers & ...
		(9, 10), CYP2D6 genotyping (11), and DNA extraction from
		Agudez J. G., Ledesma M. C., Ladero J. M., Benitez J. Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population.
		Bathum L., Johansson I., Ingelman-Sundberg M., Horder M., Brosen K. Ultrarapid metabolism of sparteine: frequency of alleles with duplicated CYP2D6 genes in a Danish population as determined by restriction length polymorphism and long polymerase chain reaction.
	cebp.aacrjournals.org /cgi/content/full/10/3/261 (1726 words)

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