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An ADHD 6-year-old child ultrarapid metabolizer for CYP2D6. Paper-12069091.
CYP2D6 competed with MAO-B for the oxidation of MPTP. Paper-12284468.
The value of CYP2D6 and OPRM1 pharmacogenetic testing for opioid therapy. Paper-13485110.
Also, the genotypes for CYP2D6, ADRB1 and GNAS1 were determined. Paper-11485189.
CYP2D6 and NAT genotypes may interact in bladder cancer. Paper-7190504.
All 16 sera from AIH-2 patients strongly bound to this CYP2D6 antigen. Paper-1037849.
In comparison, CYP2D6 genotypes were determined in POP 2 and POP 3. Paper-2081852.
CYP2D6 was colocalized with parathyroid hormone in parathyroid chief cells. Paper-9818476.
The formation of NAPQI from APAP by cDNA- expressed CYP2D6 was examined. Paper-8512711.
RESULTS: Formation of EDDP was catalysed by CYP3A4, CYP2D6 and CYP2C19. Paper-12556608.
CONCLUSIONS: IFN-beta treatment did not affect the activity of CYP2C19 or CYP2D6. Paper-9972019.
Administration of IL-10 did not alter CYP1A2, CYP2C9, and CYP2D6 activities. Paper-2100805.
Mexiletine is mainly catalyzed by CYP2D6 and partially catalyzed by CYP1A2. Paper-8700850.
A pseudogene CYP2D8P and a related gene CYP2D7 are located upstream from CYP2D6. Paper-30510.
The cytochrome P450 enzymes CYP2D6 and CYP27 are potential 25-hydroxylases. Paper-10176814.
Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. Paper-8416625.
It was shown that neither NAT2, CYP2D6 nor COMT genotype was associated with PD. Paper-13203739.
NcoI RFLP in the pseudogene ( CYP2D8P) of the human debrisoquine 4-hydroxylase locus. Paper-30793.
A genotyping for UDP-glucuronyltransferase 1A1 and CYP2D6 was followed by a re-exposure study. Paper-12860380.
Experiments in COS-7 cells showed that HNF4 could activate the CYP2D6 promoter 30-fold. Paper-710797.
Unlike other human P450s ( CYP2D6, CYP2C19) there is no evidence of a 'null' allele for CYP3A4. Paper-9636332.
The widely used beta 1-adrenoreceptor- blocking agent metoprolol is metabolized via CYP2D6. Paper-841110.
Extracellular matrix proteins modulate cytochrome P450 2D6 expression in human hepatocytes. Paper-232388.
RESULTS: CYP2D6, GST-M1 and GST- T1 were present in human parathyroid tissue. Paper-9818476.
Case-control analyses for CYP2D6, APOE, and NAT2 M1 or M2 did not show a significant association. Paper-8584214.
Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid cancer. Paper-13357717.
The CYP2D6 allele expressed in SLE patients does not have a role in CYC induced chromosomal injury. Paper-10457870.
Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers. Paper-942055.
RESULTS: CYP2D6 metabolism and HOXB13/ IL17BR gene ratio was available in 110 of 160 (69%) patients. Paper-12947728.
These data suggest that CF does not alter the activities of CYP1A2, NAT-2, XO, and CYP2D6. Paper-10210291.
Recently, new advances in our knowledge of the CYP2D6 gene and its locus ( CYP2D) have been achieved. Paper-1376556.
Lack of mutations in CYP2D6 and CYP27 in patients with apparent deficiency of vitamin D 25-hydroxylase. Paper-10176814.
The debrisoquine 4-hydroxylase activity was not significantly changed by alpha1- AGP or gamma-globulins. Paper-8701508.
Such activity is NADPH dependent and is inhibited by quinidine and CYP2D6-specific substrates. Paper-1077670.
These results demonstrate that SCH 66712 is a potent and fairly selective mechanism-based inhibitor of CYP2D6. Paper-8962449.
An oligo/monoclonal antibody thus generated gave both the typical fluorescent pattern and reacted with CYP2D6. Paper-8201804.
CSF taurine level is influenced by plasma cholesterol and the CYP2D6 phenotype. Paper-9969034.
Four polymorphisms (Tp53, IL-10, CYP2D6 and the MTHFR) exhibited an increased CIN and cervical cancer risk. Paper-10782092.
Rapid genotyping of CYP2D6, CYP2C19 and TPMT polymorphisms by primer extension reaction in a dipstick format. Paper-12633506.
Amplification of CYP1A1, CYP1A2, CYP2A6, CYP2D6, CYP2F1, CYP3A7, and CYP19 was not found. Paper-1384929.
CONCLUSIONS: The presence of CYP2D6, GST-M1 and GST- T1 in parathyroid cells was observed. Paper-9818476.
CYP2C9 coincubation had no effect on CYP2D6-mediated dextromethorphan O-demethylation. Paper-13780267.
Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Paper-12822459.
CYP3A4 showed the highest progesterone 16 alpha-hydroxylation activity, followed by CYP1A1 and CYP2D6. Paper-1558447.
HTR3A gene polymorphisms and the CYP2D6 gene polymorphisms had no significant effect on the incidence of nausea. Paper-12246459.
Previous studies indicated an association of debrisoquine hydroxylase ( CYP2D6) with susceptibility to epilepsy. Paper-12316573.
Paroxetine substantially inhibits CYP2D6 but doses not appear to inhibit any other CYP enzyme. Paper-1014921.
With expressed P450 isoforms, hydrastine formed a P450 MI complex with CYP2C9, CYP2D6, and CYP3A4. Paper-10102254.
There was no association between the studied polymorphisms of CYP1A2, CYP2D6, GSTM1, and GSTP1 genes and BC. Paper-13531459.
Whereas DEP was N-demethylated and N-depropargylated by the CYP2D6 enzyme system, no metabolites were formed from BPA. Paper-8498621.
Just 4 genes together accounted for nearly one-fifth of all publications: ABCB1, CYP2C9, CYP2C19, and CYP2D6. Paper-13609459.
Using the 2(-Delta Delta Ct) calculation method and a duplex reaction, the number of CYP2D6 gene copies was determined. Paper-11470049.
Candidate genes tested included estrogen receptor 1 ( ESR1), CYP genes ( CYP2C9 and CYP2D6) and STK11. Paper-12963089.
The aim of this study was to search for antibodies against CYP2D6 conformational antigenic sites in LKM-1-positive sera. Paper-157511.
Here, we report the identification of a novel coding variant of HNF4A that influences CYP2D6 activity in humans. Paper-12897636.
CONCLUSIONS: We conclude that there are no differences between Black subjects and White subjects in metabolism via CYP2D6. Paper-725104.
Effect of the CYP2D6 genotype on prolactin concentration in schizophrenic patients treated with haloperidol. Paper-9024329.
Metabolism of dextromethorphan in human liver microsomes: a rapid HPCL assay to monitor cytochrome P450 2D6 activity. Paper-782242.
Association of low CYP3A activity with p53 mutation and CYP2D6 activity with Rb mutation in human bladder cancer. Paper-558459.
Blood was also obtained for determination of serum insulinlike growth factor-1 ( IGF-1) levels and CYP2D6 genotype. Paper-13025600.
Genotypes at GSTM1, GSTT1, and the cytochrome P450 CYP1A1 and CYP2D6 loci were also determined. Paper-532645.
MDR-1 genotypes (C3435T and G2677T/A) and CYP2D6 genotypes were identified using PCR-RFLP methods. Paper-10354435.
Lung cancer and CYP2D6 (the debrisoquine polymorphism): sources of heterogeneity in the proposed association. Paper-392124.
The polymorphism of dextromethorphan ( CAS 125-71-3) metabolism is dependent on hepatic cytochrom P4502D6 ( CYP2D6) activity. Paper-181586.
These results strongly suggest that antibodies against CYP2D6 conformational antigenic sites were present in LKM-1-positive sera. Paper-157511.
Clozapine appears to be metabolized primarily by CYP1A2 and CYP3A4, with additional contributions by CYP2C19 and CYP2D6. Paper-1957987.
CYP17, SRD5A2, CYP1B1, and CYP2D6 gene polymorphisms with prostate cancer risk in North Indian population. Paper-12014627.
The major target of LKM-1 antibodies is cytochrome P450 2D6; a second less frequent target was the described UGTs of family 1. Paper-1033152.
Subsequently, MRP of maprotiline (4.9) and CLM were reduced (1900 ml.min-1; expected CLM in poor metabolisers: of CYP2D6 364). Paper-1149621.
Addition of the radical scavenger DMSO increased levels of CYP2D6 holoenzyme in DUKX/2D6/ CPR-3 cells but not in DUKX/2D6 cells. Paper-8966981.
Frequency, IFN-gamma production, and cytotoxicity of CYP2D6-specific CD8 T cells were higher at diagnosis than during treatment. Paper-13367025.
Microsomal protein expression of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 tended to decrease with NAFLD progression. Paper-14001706.
Frequencies of GSTM3, GSTM1, GSTT1, CYP2D6, and CYP1A1 genotypes in the cases and controls were not different. Paper-532645.
Rate of cognitive decline in Alzheimer's disease is not affected by the alpha-1-antichymotrypsin A allele or the CYP2D6 B mutant. Paper-886949.
However, DOM and/or other metabolites such as deamino-oxo-hydroxy DOM might be the target analyte in urine of CYP2D6 poor metabolizers. Paper-12721791.
CYP2D6 coincubation inhibited CYP2C9-mediated ( S)-flurbiprofen metabolism in a protein concentration-dependent manner. Paper-13780267.
Epitope mapping studies had previously been performed for CYP2D6, CYP17, CYP21A2, and recently for CYP3A1 and CYP2C9. Paper-1116797.
Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Paper-12821874.
Combined tests for anti- CYP2D6 radioligand assay and anti- arginase antibodies resulted in detection of 55% of AIH patients. Paper-9284624.
When CYP2D6 index and anti- arginase antibodies were combined, 55.3% of AIH patients were positive for either one or both antibodies. Paper-9284624.
Escitalopram is metabolised by the cytochrome P450 ( CYP) isoenzymes CYP2C19, CYP2D6 and CYP3A4. Paper-12465947.
CONCLUSION: This study has identified a number of genes requiring further investigation including EPHX1, ADPRT1, CYP2D6, and AhR. Paper-11024449.
We now present evidence which demonstrates that human cytochrome P450 2D6 ( CYP2D6) is also involved in the bioactivation of APAP. Paper-8512711.
So, we have used the same benchmarking procedure with the HERG channel and CYP2D6 enzyme, for which a minimal affinity is strongly desired. Paper-13031261.
However, very limited data are available on the influence of cyclooxygenase 2 inhibitors on the disposition of CYP2D6 substrates in humans. Paper-9794761.
Furthermore, human subjects with the HNF4A G60D genotype tended to have lower CYP2D6 activity than those with the wild-type HNF4A. Paper-12897636.
Furthermore, HPTP and reduced-HPTP, of comparable lipophilicity to the N-heptyltetrahydropyridine analog were inactive as CYP2D6 substrates. Paper-10020332.
CYP2C9 and CYP2C19 provided enhanced formation of R-EDDP and CYP2D6 incubation resulted in the preferential conversion to S-EDDP. Paper-9964806.
Fluvoxamine inhibits with decreasing potency, CYP1A2, CYP2C19, CYP2D6 and CYP1A1, but it is also an inhibitor of CYP3A. Paper-913359.
Our results indicate that several SNPs in the Phase I genes CYP1B1, CYP2D6, CYP2E1 and CYP3A4, are associated with risk of NSCLC. Paper-12774741.
The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN-beta. Paper-9972019.
The frequency of homozygous for CYP2D6 inactive alleles or poor metabolizers (PMs) was lower (P<0.05) in SP than in HV. Paper-12622905.
The aim of the present study was to characterize anti- CYP2D6 cellular immune responses and their possible pathogenic role in patients with AIH-2. Paper-10839022.
The addition of antioxidant increased V(max) for CYP2C9 and CYP2D6 by 75 and 50%, respectively, whereas V(max) for CYP3A4 was unchanged. Paper-9574940.
The data demonstrate site-dependent associations between GSTT1 null, CCND1 GG, and CYP2D6 PM and tumor extension, differentiation, and nodes. Paper-8286304.
AIMS: To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis ( MS) before and during interferon (IFN)-beta treatment. Paper-9972019.
These data demonstrate that classic histamine H1 receptor antagonists, available in over-the-counter preparations, inhibit CYP2D6 in vitro. Paper-1460310.
Mutation of the HNF4 binding site in the CYP2D6 promoter partially restored the suppression of the promoter activity by NO donors. Paper-9348879.
A week before the initiation of omeprazole the activities of CYP2D6, CYP2C19, and CYP3A4 were determined by previously established methods. Paper-690493.
In contrast, none of the compounds examined significantly increased levels of CYP2C8, CYP2C9, CYP2D6, CYP2E1, and CYP4A11 apoproteins. Paper-9792221.
MPTP oxidation by MAO-B to MPDP(+) and MPP(+) toxins (bioactivation) was up to 3-fold higher than CYP2D6 detoxification to PTP and MPTP-OH. Paper-12284468.
We used three cell lines and CD-1 mice to assess the activity of genomic promoter sequences of human CYP2D6, 1A2, 3A4, 2C9, 2C18, and 2E1 genes. Paper-12181365.
Fluoxetine substantially inhibits CYP2D6 and probably CYP2C9/10, moderately inhibits CYP2C19 and mildly inhibits CYP3A3/4. Paper-1014921.
Polymorphisms of genes CYP2D6, ADRB1 and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study. Paper-11485189.
Each serum sample was assayed for reactivity against formiminotransferase cyclodeaminase and CYP2D6 alone or as part of a recombinant chimera protein. Paper-9446727.
Moreover, mexiletine inhibits CYP2D6- mediated metabolism of metoprolol and cytochrome P450 1A2-mediated metabolism of theophylline. Paper-1684015.
Molecular mimicry between HCV proteins and CYP2D6 has been proposed to explain the emergence of these autoantibodies. Paper-11037307.
The two livers with the highest proportion of CYP2D6- mediated N-dealkylation had relatively high ratios of specific CYP2D6 to CYP1A2 activity. Paper-816603.
The high prevalence of the poor and ultrarapid metabolite alleles of CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 in Taiwanese population. Paper-11988529.
SP and HV with >2, 2, 1 or 0 CYP2D6 active genes were 4.7, 64.8, 28.1 and 2.3%, and 6.3, 52.1, 33.1 and 8.5%, respectively. Paper-12622905.
Risk associated with PON1 genotype and phenotype varied with CYP2D6 and GSTP1 genotype but not consistently with a priori hypotheses. Paper-13267091.
CYP2D6 catalyzed diphenhydramine N-demethylation as a high-affinity P450 isozyme, the K(m) value of which was 1.12 +/- 0.21 microM. Paper-12385888.
The experimental binding energies (DeltaG(bind)) were calculated for MAA with CYP1A1 and CYP2D6 to be -8.266 and -7.074 kcal/mol, respectively. Paper-12385895.
Dealkylation was mainly catalyzed by CYP2B6 and CYP2C19, demethylenation was additionally catalyzed by CYP1A2, CYP2D6, and CYP3A4. Paper-13760369.
POP 1 patients were evaluated before and after 21 or more days of treatment with antipsychotic drugs metabolized at least in part by CYP2D6. Paper-2081852.
The CYP2D6 gene on human chromosome 22 encodes a cytochrome P450 responsible for oxidative metabolism of over 30 clinically used drugs. Paper-903480.
The activities of two other major drug-metabolizing enzymes ( cytochrome P450 3A4 and 2D6 [ CYP3A4 and CYP2D6]) were also measured in these 17 patients. Paper-585854.
OBJECTIVE: The objective of this study was to determine whether metabolism via cytochrome P4502D6 ( CYP2D6) was higher in Black subjects than White subjects. Paper-725104.
The HPF1 binding sequence is conserved in CYP2A, CYP2C, and CYP2D genes and resembles the binding motif for hepatic nuclear factor-4. Paper-7526804.
Therefore, the current study was undertaken to characterize the in vitro inhibition of CYP2D6 by these commonly used, histamine H1 receptor antagonists. Paper-1460310.
Synergistic Use of Compound Properties and Docking Scores in Neural Network Modeling of CYP2D6 Binding: Predicting Affinity and Conformational Sampling. Paper-12332264.
No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase ( CYP2D6) and the dopamine transporter ( DAT). Paper-410518.
4. It is concluded that formation of tamsulosin metabolites, AM-1 and M-1, is catalysed by CYP3A4 whereas that of M-3 and M-4 is catalysed by CYP2D6. Paper-1731060.
In this study we examine the role of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk in Brazilian women. Paper-12878845.
The aim of this study was to investigate the association between the CYP2D6 poor metaboliser genotype and the risk of papillary thyroid cancer ( PTC). Paper-13357717.
CONCLUSIONS: Endoxifen is an active tamoxifen metabolite that is generated via CYP3A4- mediated N-demethylation and CYP2D6-mediated hydroxylation. Paper-10167236.
In human experimental studies, we have shown that CYP phenotype and genotype affect abuse liability of CYP2D6 metabolized drugs of abuse. Paper-8412807.
Antidepressants are metabolized by and are competitive inhibitors of several isoenzymes: CYP1A2, CYP2D6, CYP3A3/4, CYP2C8/9, CYP2C19, and others. Paper-744634.
SCH 66712 [5-fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyrimidine] caused a time- and NADPH-dependent loss of CYP2D6 activity. Paper-8962449.
In addition, only CYP2D6 of several cDNA- expressed human CYP enzymes examined showed substantial activity for the formation of fluvoxamino alcohol. Paper-13225031.
Combined phenotypic assessment of CYP1A2, CYP2C19, CYP2D6, CYP3A, N-acetyltransferase-2, and xanthine oxidase with the "Cooperstown cocktail". Paper-8472936.
The studies showed a moderate risk for BP-11 for interactions with the cytochrome P-450 isoenzymes CYP1A2, CYP2C9, CYP2D6 and CYP3A4. Paper-12154655.
Although CYP2D6 is essentially an uninducible enzyme in the liver, we show that smokers have higher CYP2D6 in the brain, especially in the basal ganglia. Paper-13057568.
The expanded panel of assays, however, failed to document CYP2D6 as the target autoantigen of anti-liver-kidney microsomal autoantibodies in most patients. Paper-9189347.
CYP3A5 genotype did not appear to influence haloperidol half-life but the two CYP2D6 poor metabolizer had half-lives > or =3 days. Paper-10888384.
Concurrent oral use of CYP2D6 substrates with MPPP and PEPAP may represent a kinetic drug interaction risk, but this risk must be confirmed clinically. Paper-9458254.
Diverse Structures of Chimeric CYP-REP7/6-Containing CYP2D6 and a Novel Defective CYP2D6 Haplotype Harboring Single-type *36 and CYP-REP7/6 in Japanese. Paper-12293233.
CYP2D6 possessed highest intrinsic (-)-OSU6162 N-depropylase activity when compared with a battery of recombinant heterologously expressed human p450 enzymes. Paper-9648826.
Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Paper-12477158.
The aim of the present study was to evaluate the contribution of MAOB, COMT, NAT2 and CYP2D6 gene polymorphisms to early onset Parkinson's disease (PD). Paper-13203739.
The method was evaluated by genotyping two SNPs of the human mannose-binding lectin gene ( MBL2) and one SNP of the cytochrome P450 gene CYP2D6. Paper-13352527.
Typical P450 CO-difference spectra with absorbance maximum at 448 nm were recorded with microsomal preparations from the yeast cells expressing the four CYP2D forms. Paper-1297315.
Fluvoxamine has prominent affinity for the CYP12 isozyme, lesser affinity for the CYP3A4 and CYP2C isozymes, and minimal affinity for CYP2D6. Paper-1029717.
NQO1 null (P = 0.001) and MC1R asp294/asp294 (P = 0.03) were linked with BCC numbers, and the association with CYP2D6 EM approached significance (P = 0.08). Paper-1944359.
Multiple night-time doses of valerian ( Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Paper-10867501.
Tam metabolism by CYP2D6 coexpressed with P450 reductase in a baculovirus infected insect cell line ("supersomes") exhibited marked tam 4-hydroxylation. Paper-1128590.
4. This work suggests that quinidine is a non-classical inhibitor of CYP1A1 and that it is not as highly specific at inhibiting CYP2D6 as previously thought. Paper-9149731.
The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. Paper-11815931.
We prospectively evaluated significance of CYP2D6 genetic variation for prolactin response to perphenazine (a model first-generation antipsychotic) in Asians. Paper-13180559.
Lung cancer risks for the CYP2D6 PM genotype amongst light smokers (tobacco consumption </=20 g/day) or heavy smokers (>20 g/day) were not significantly different. Paper-8609010.
The potential role of CYP2E1 and CYP2D6 in NNK- induced genetic damage in cultured human lymphocytes was characterized using specific CYP inhibitors. Paper-8459390.
On searching the literature, it is obvious that this reaction is far less common among cytochrome P450 2D6 catalyzed reactions compared with other cytochromes P450. Paper-13044337.
Microsomes of B-lymphoblastoid cells expressing human CYP1A2 exhibited lower mexiletine p- and 2-hydroxylase activities than those expressing human CYP2D6. Paper-1567438.
Debrisoquine metabolism is controlled by a cytochrome P-450 isozyme encoded at the CYP2D6 locus, which is inducible by antipyrine and rifampicin. Paper-8021641.
These results demonstrated that NO down-regulates CYP2D6 gene expression, at least in part, by directly inhibiting HNF4 binding to the CYP2D6 promoter. Paper-9348879.
METHODS: We assessed the effect of TJ-19 on the activities of CYP1A2, CYP2D6, CYP3A, xanthine oxidase (XO), and N-acetyltransferase 2 ( NAT2) in 37 healthy subjects. Paper-13143855.
Genetic polymorphisms in CYP1A1, CYP2D6, UGT1A6, UGT1A7, and SULT1A1 genes and correlation with benzene exposure in a Chinese occupational population. Paper-13221332.
CYP2D6 catalysed the demethylenation with apparent Km and Vmax values of 13.5+/-1.5 microM and 1.3+/-0.1 pmol/min/pmol CYP, respectively. Paper-11041028.
Our data thus provide evidence that the 2- and 8-hydroxylation of clomipramine are catalyzed by CYP2D6 and that the N-demethylation is catalyzed in part by CYP2C. Paper-8206485.
Phenotype/ genotype relationships for the cytochrome P450 enzyme CYP2D6 in rheumatoid arthritis: influence of drug therapy and disease activity. Paper-133120.
Compounds from this series exhibited considerable binding affinity (Ki = 1 nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure. Paper-12174565.
Incubation of 2 microM MPPP with 3 microM of the CYP2D6-specific inhibitor quinidine resulted in significant (p < 0.01) turnover inhibition (11.8 +/- 1.6% of control). Paper-9930665.
Blood samples were genotyped for DRD2 Taq1 A, Ins/Del and Ser311Cys, HTR2A T102C, HTR2C Cys23Ser, ABCB1 1236C>T, 2677G>T/A, 3435C>T and genetic variants of CYP2D6. Paper-13085529.
Preliminary studies showed that tamoxifen had no effect on the activities of CYP1B1 and CYP3A4, whereas CYP2D6 and CYP2C9 exhibited a 25% loss in enzymatic activity. Paper-9209694.
Formation of APNH was observed with CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2D6, CYP2E1 and CYP3A4, but not with CYP2A6, CYP2C9 and CYP2C19. Paper-10477000.
Susceptibility to astrocytoma and meningioma: influence of allelism at glutathione S-transferase ( GSTT1 and GSTM1) and cytochrome P-450 ( CYP2D6) loci. Paper-354303.
These data suggest that in control mice CYP2E1 catalyzes the bulk of protein binding, whereas CYP2D catalyzes slightly more cysteine conjugation than does CYP2E1. Paper-1020477.
The decline in CYP3A4 and CYP2D6 activity might have clinical implications when substrates of these enzymes with low therapeutic indices are combined with somatostatin analogs. Paper-1559041.
CYP2C19 alleles *1 to *5 and CYP2D6 alleles *1 to *12, and *14, *15, and *17 were measured by polymerase chain reaction-restriction fragment length polymorphism assays. Paper-1957068.
Cytochrome P450 2D6 and homeobox 13/ interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistance. Paper-12947728.
We sought to determine the combined effect of inherited ( CYP2D6) and somatic ( HOXB13/ IL17BR) gene variation in tamoxifen-treated breast cancer. Paper-12947728.
Based on kinetic data corrected for the relative activity factors, CYP2D6 is the enzyme mainly responsible for MPPP hydroxylation, confirmed by CYP2D6 inhibition studies. Paper-9930665.
Therefore, the contribution of the DR1 element in controlling the transcription of the CYP2D6 gene depends on the balance between positively and negatively acting transcription factors. Paper-710797.
Azelastine did not inhibit CYP3A4 activity but it did inhibit CYP2D6 and CYP2C19 activity with Ki values exceeding maximum plasma concentration by 120 to 800-fold. Paper-1353498.
CONCLUSION: This is the first report to show that the genetic polymorphism of liver-enriched nuclear receptor HNF4A influences downstream CYP2D6 function in human subjects. Paper-12897636.
Further, CYP2D6 is expressed in the human brain as a 5-methoxyindolethylamine O-demethylase potentially contributing to regeneration of serotonin from 5-methoxytryptamine. Paper-13180559.
No significant difference in the ratio of DC/ HDC was observed between subjects who were homozygous for mutated alleles of CYP2D6 and those who were homozygous for wild-type alleles. Paper-9148520.
The expression of CYP1A2 and CYP2D6 mRNA were not affected by the introduction of hPXR-siRNA, suggesting that PXR plays no functional role in the expression of either of these genes. Paper-13429789.
CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Paper-12501055.
METHODS: One polymorphism at DRD2 gene, five at DRD3, 24 at CYP2D6, nine at CYP3A4 gene, and one at CYP3A5 gene were genotyped in a sample of 186 patients with schizophrenia. Paper-12831261.
METHODS: Methadone was incubated with various drugs (n = 10) and cDNA-expressed CYP3A4, CYP2D6, CYP2B6, CYP2C19 and CYP1A2 enzymes to screen for their inhibition potency. Paper-12556608.
Formation of the nevirapine GSH conjugate was primarily catalyzed by heterologously expressed recombinant CYP3A4 and, to a lesser extent, CYP2D6, CYP2C19, and CYP2A6. Paper-13847912.
A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory profiles has been identified. Paper-11340885.
Although the type of ADR was, as expected, different between drugs, the frequency of ADRs experienced did not differ significantly between the two antidepressants or between CYP2D6 PMs and EMs. Paper-10267093.
Our previous study using a panel of recombinant cytochrome P450 ( P450) enzymes suggests that pinoline O-demethylation may be selectively catalyzed by polymorphic CYP2D6. Paper-13622708.
The CYP3A4 inhibitors ketoconazole and troleandomycin decreased microsomal DTZ oxidation, but inhibitors or substrates of CYP2C, CYP2D and CYP2E1 produced no inhibition. Paper-1090718.
Summed lod scores for all families excluded linkage to the genes GPX1, TH, APP, SOD1, and CYP2D6, as well as to the chromosomal region containing the genes CAT and BDNF. Paper-130907.
Coadministration of codeine with selective inhibitors of CYP3A4 may result in increased morphine production and enhanced pharmacodynamic effects due to shunting down the CYP2D6 pathway. Paper-927334.
No differences in genetic predisposition were found between MS patients exposed and those not exposed to organic solvents regarding GSTM1 null or CYP2D6 poor metaboliser genotypes. Paper-10063211.
CONCLUSIONS: Variable plasma concentrations of carvedilol during long-term administration are predicted by CYP2D6 genotype and intestinal expression of P-glycoprotein and MRP2. Paper-10212755.
These results suggest that CYP1A2 catalyzes NdM olanzapine and 7-OH olanzapine formation, CYP2D6 catalyzes 2-OH olanzapine formation and FMO3 catalyzes N-O olanzapine formation. Paper-548732.
After correction for the loss of activity between the methods, the intrinsic activities of hepatic and intestinal CYP3A4, CYP2C9, CYP2C19, and CYP2D6 were comparable for the 16 pathways. Paper-12184758.
Search for these determinants has led to a few consensus associations of CYP2D6 *10, CYP1A2*1F, DRD2 Taq1A (rs1800497), DRD3 Ser9Gly (rs6280) and MnSOD Ala9Val (rs4880) variants with TD. Paper-12992786.
Kinetic constants for CYP2D6 N-dealkylation of MAA and EAA were K(m) 7.9 +/- 5.4 and 3.2 +/- 1.6 microM, and V(max) 501 +/- 35.4 and 702.7 +/- 257 pmol 9AA/min/pmol CYP2D6, respectively. Paper-12385895.
10. CYP2D6 polymorphism has been associated with the risk of onset of various illnesses, including cancer, schizophrenia, Parkinson's disease, Alzheimer's disease, and epilepsy. Paper-1884393.
However, the Km values of the expressed CYP1A2 (approximately 15 microM) were almost identical with those of the expressed CYP2D6 (approximately 22 microM) and human liver microsomes. Paper-1567438.
Oxybutynin inhibited CYP3A4- and CYP2D6- associated activities ( testosterone 6 beta-hydroxylase and dextromethorphan O- demethylase, respectively) in human liver microsomes. Paper-1449985.
RESULTS: Smurf2, FGG, PTAFR, CYP2D6, among others, increased in the fibrosis liver and a semi-quantitative RT-PCR confirmed the reliability of the cDNA microarray analysis. Paper-12282172.
Mice expressing human CYP1A1/ CYP1A2, CYP2E1, CYP2D6, CYP3A4, CY3A7, pregnane X receptor, and peroxisome proliferator-activated receptor alpha were generated and characterized. Paper-13043696.
A CYP2D6 fusion enzyme (CYP2D6F), containing an amino-terminal human CYP2D6 sequence and a carboxyterminal human NADPH- cytochrome P450 oxidoreductase ( CPR) moiety, was constructed. Paper-8858153.
In one sample, a previously unreported 3201C 224 T transition in exon 7 resulted in Arg344(CGA) being replaced by a stop codon ( TGA), resulting in a CYP2D6 enzyme lacking the terminal 153 amino acids. Paper-12147207.
OBJECTIVES: The objectives are to determine whether IFN-alpha and ribavirin can alter pretreatment CYP1A2, CYP2D6, CYP3A4 and N-acetyltransferase-2 activities after 1 month of treatment. Paper-9496621.
OBJECTIVE: To assess the effect of cyclophosphamide (CYC) and the influence of CYP2D6 polymorphism on micronuclei expression in patients with systemic lupus erythematosus ( SLE). Paper-10457870.
The cytogenetic assignment of SP1, IGFBP6, COL2A1, IGF1, MB and CYP2D6 is first reported here and the assignment of HOXC4 refines the previous assignment of this gene. Paper-10178289.
Polymerase chain reaction and restriction fragment length polymorphism analyses were used to detect inactivating mutations in the CYP2D6 gene and assign genotype in all 116 individuals. Paper-89986.
Microsomes from six CYP2D6 extensive metabolizers and one CYP2D6 poor metabolizer were used with isoform specific chemical and antibody inhibitors and expressed recombinant CYP enzymes. Paper-10923235.
Expression of recombinant CPR decreased the level of spectrally detectable CYP2D6 holoprotein in DUKX/2D6/ CPR-3 cells by 70%, whereas the level of immunodetectable apoprotein remained unchanged. Paper-8966981.
We investigated whether ALL outcome was related to polymorphisms in genes CYP2D6, MPO, EPHX1, NQO1, TS, XPD and XRCC1 in 95 consecutive ALL children by PCR or PCR-FRLP techniques. Paper-13752871.
Anti-LKM-1 autoantibodies are directed mostly at cytochrome P450 2D6 ( CYP2D6) autoantigen, whose activity ranges from "complete deficiency" to "extensive metabolism" due to genetic polymorphism. Paper-8491786.
According to the manufacturer, the CYP2D6 genotype or drugs that influence CYP2D6 or other cytochrome P450 isoenzyme activity are not expected to be clinically significant. Paper-1950276.
Among them, CYP2D6 is thought to be the major target autoantigen to anti-liver kidney microsome (LKM)-1 autoantibody, a characteristic feature of autoimmune hepatitis ( AIH) type II. Paper-8555717.
Molecular analysis was performed for the CYP2 family of Cytochrome P450 ( CYP450) drug metabolism isoenzymes by DNA typing CYP2D6, CYP2C9, and CYP2C19 genes. Paper-13227068.
Human liver specimens with the heterozygous HNF4A G60D genotype showed a tendency toward lower levels of CYP2D6 activity than the wild-type genotype in the same genetic background of CYP2D6. Paper-12897636.
In addition to cytochrome P450 2D6, which plays a critical role in drug metabolism, ABCB1 encoded P-glycoprotein ( PGP) is also an important determinant in drug bioavailability. Paper-13814211.
All are eliminated from the body via metabolism involving principally CYP3A4 and the highly polymorphic CYP2D6, which markedly affects the drug's function, and by conjugation reactions mainly by UGT2B7. Paper-13589386.
In this study, human lymphocyte activity was assessed with a CYP2D6-specific, high-turnover probe substrate that is severalfold more sensitive than traditional markers of CYP2D6 (e.g., dextromethorphan). Paper-9958567.
Additionally, COUP-TFI was shown to inhibit HNF4 stimulation of the CYP2D6 promoter in COS-7 cells, suggesting that COUP-TFI could attenuate the effect of HNF4 in HepG2 cells. Paper-710797.
Our method resulted in five biomolecules that may provide a link between the antipsychotic agents and cancer: brain-derived neurotrophic factor, CYP2D6, glucocorticoid receptor, PRL, and TNF. Paper-13465012.
Except 3 which inhibited CYP1A2 isoform by more than 50% none of the other compounds inhibited key cytochrome P450 enzyme isoforms ( CYP1A2, CYP2C9, CYP2D6 and CYP3A4) at 10 muM. Paper-12688609.
Assessment of CYP1A2, NAT2, XO, CYP2D6, and CYP3A4 activities was performed before and at the end of the study period, using caffeine, dextromethorphan, and endogenous cortisol as probes. Paper-10210432.
Polymerase chain reaction was used to determine A-1438G of the 5-HT2A receptor, C195T and Pro16Ser of the 5-HT3A receptor, Tyr129Ser of the 5-HT3B receptor, and the *5 and *10 alleles of CYP2D6. Paper-11406664.
CONCLUSIONS: Botanical supplements containing goldenseal strongly inhibited CYP2D6 and CYP3A4/5 activity in vivo, whereas kava inhibited CYP2E1 and black cohosh weakly inhibited CYP2D6. Paper-11095137.
Functional allelic variant frequencies in genes encoding carcinogen-metabolizing enzymes GSTT1, GSTM1, CYP1A1, CYP2D6, CYP2C19, SULT1A1, and NQO1 were previously determined for this cohort. Paper-9667337.
PCR amplifications of specific sequences of p53, p16, CYP1A1, CYP2D6, GSTM1 and GSTM3 were performed independently on the same strips of uncharged nylon membrane containing genomic DNA. Paper-1157893.
For the polymorphisms in EDH17B2, ER, CYP2D6, CYP2E1, GSTT1, HSP70, and TNFalpha, the risk estimates, although nonsignificant, were insufficiently precise to exclude a moderate risk (>1.5). Paper-8337961.
CONCLUSIONS: In this study, we identified SNPs in LIG4, ERCC2, and CYP2D6 genes as putative markers to predict individuals at risk for complications arising from radiation therapy in prostate cancer. Paper-11824054.
STUDY DESIGN: The method of deoxyribonucleic acid isolation, sample preparation, oligonucleotide primers, and polymerase chain reaction procedures were scrutinized for their effect on CYP2D6 genotyping efforts. Paper-770504.
It includes the amplification of 2 CYP2D6 and 7 control ( AQP1, CYP3A4, MDR1, and SDHB) fluorescent PCR products that are separated on a capillary sequencer and normalized using reference samples. Paper-13741266.
A novel approach to predicting P450 mediated drug metabolism. CYP2D6 catalyzed N-dealkylation reactions and qualitative metabolite predictions using a combined protein and pharmacophore model for CYP2D6. Paper-8303303.
We used marker enzyme activity levels, diagnostic inhibitors and immunoblot analysis to assess members of the CYP2A, CYP2B, CYP2C, CYP2D, CYP2E and CYP3A sub-families. Paper-8733477.
The K(m) for dextromethorphan N-demethylation by Cyp2d22 was found to be 418 microM, much lower than that observed with human CYP2D6 and near the K(m) for dextromethorphan N-demethylation catalyzed by CYP3A4. Paper-12046068.
3. The calculated percent inhibition by olanzapine of substrates metabolized by CYP3A, CYP2D6, CYP2C9, and CYP2C19 was modeled assuming a total plasma concentration in the therapeutic range (0.2 microM). Paper-759253.
The aim of this study is to identify the high prevalence (minor allele frequencies >1%) of the abnormal metabolite alleles of CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Taiwanese population. Paper-11988529.
It is postulated that the difference in the antiemetic efficacy between two investigated 5-HT3 receptor antagonists may be associated with differences in the carrier status for the duplication of the CYP2D6 allele. Paper-11359586.
SCH 66712 also inhibited HL microsomal CYP3A4, CYP2C9, and CYP2C19; however, the concentrations required to inhibit those isoforms were 5- to 10-fold higher than those required to inhibit CYP2D6. Paper-8962449.
Polymorphism of CYP2D6 gene encoding for debrisoquine hydroxylase was determined genotypically for 94 controls and 77 lung cancer patients using a polymerase chain reaction-based application. Paper-116778.
A subgroup of 10-15% of Caucasians are termed phenotypical 'intermediate metabolizers' of drug substrates of CYP2D6 because they have severely impaired yet residual in-vivo function of this cytochrome P450. Paper-8551449.
Nearly 50% of all medications currently on the market are metabolized by the enzyme CYP3A4, while metabolism of another 35-40% occurs through enzymes CYP1A2, CYP2C19, CYP2D6, CYP3A5 CYP3A6, and CYP3A7. Paper-11533188.
PURPOSE: It has been reported that carvedilol, which has beta-adrenergic blocking and vasodilating activities, is mainly metabolized by UDP-glucuronosyltransferase ( UGT) 1A1, UGT2B4, UGT2B7 and CYP2D6. Paper-12067409.
The polymerase chain reaction was used to amplify cDNA from a human caudate lambda gt11 library encoding exons 6-9 of the human CYP2D6 gene, which revealed, upon sequencing, 100% nucleic acid sequence identity. Paper-7151383.
Recent studies have suggested that HNF4A regulates the expression of cytochrome P450 ( CYP), including CYP2D6 and CYP3A4, which show large individual variations in their activities. Paper-12897636.
We conclude from these studies that the formation of 5-HM is catalyzed by CYP2D6 and that the formation of N-dealkylated tolterodine is predominantly catalyzed by CYP3A isoenzymes in human liver microsomes. Paper-1403850.
The results from in vitro experiments with recombinant isoforms and P450 isoform-selective inhibitors suggested that the oxidative metabolism of lasofoxifene is catalyzed primarily by CYP3A and CYP2D6. Paper-12842003.
METHODS: Genotyping for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, ABCB1, and UGT2B7 polymorphisms was performed in 245 patients undergoing methadone maintenance treatment. Paper-12412925.
To investigate the involvement of the CYP17, SRD5A2, CYP1B1, and CYP2D6 variants with prostate cancer, a case-control study of 100 patients and an equal number of age-matched control men was conducted. Paper-12014627.
Addition of quinidine, a reversible inhibitor of CYP2D6, to a preincubation mixture consisting of SCH 66712, HL microsomes, or Supersomes and NADPH partially protected CYP2D6 from inactivation. Paper-8962449.
P450 reaction phenotyping using recombinant cDNA- expressed human CYPs in conjunction with specific CYP inhibitors indicated that CYP2D6 and CYP2C19 were the predominant CYPs involved in SQ109 metabolism. Paper-11317917.
Cytochrome P4502D6 ( CYP2D6), target of liver kidney microsomal autoantibody type 1 (LKM1), characterizes autoimmune hepatitis type 2 ( AIH2) but is also found in patients with chronic hepatitis C virus (HCV) infection. Paper-9823764.
We show that testosterone inhibited the CYP2D6- mediated bufuralol 1'-hydroxylase activity in bacterial membranes containing both CYP2D6 and CYP3A4 but not in membranes containing CYP2D6 alone. Paper-1832121.
OBJECTIVES: This study aimed to explore the influence of variation in DRD2, DRD3, CYP2D6, CYP3A4, and CYP3A5 genes on treatment resistance to typical neuroleptics in a Brazilian sample of patients with schizophrenia. Paper-12831261.
Conversely, bufuralol inhibited the CYP3A4- mediated testosterone 6beta-hydroxylase activity in bacterial membranes containing both CYP3A4 and CYP2D6 but not in membranes containing only CYP3A4. Paper-1832121.
OBJECTIVE: To assess the impact of CYP2C9 polymorphisms and of the CYP2D6 poor metaboliser genotype on the pharmacokinetics of nateglinide and its effects on insulin, glucose and glucagon in plasma. Paper-10288594.
We describe the role of allelism at the glutathione S-transferase GSTM1, GSTM3, GSTT1 and cytochrome P450 CYP1A1, CYP2E1, CYP2D6 loci in determining individual susceptibility to laryngeal SCC. Paper-1007705.
Epitope mapping experiments were performed by a series of truncated CYP2D6 proteins and by single epitopes of 257-269, 321-351, 373-389 and 410-419 amino acid (aa) expressed as DHFR-fusion proteins in Escherichia coli. Paper-10693138.
Convincing evidence of functional relevance exists for polymorphisms in genes such as CYP2D6 and UGT1A1, whereas the published evidence for similar effects for CYP3A5, OATP1B1, and ABCB1 is still emerging or equivocal. Paper-11338599.
The expression of cytochrome P450 ( CYP) 1A1 and CYP1A2 mRNA, but not CYP2D6, CYP3A4, and CYP2C9 mRNA, was increased in beta-NF-treated Caco-2 cells, as compared with non-treated cells. Paper-13639631.
Milnacipran oxidative metabolism is not mediated through CYP2D6 or CYP2C19 polymorphic pathways nor does it significantly interact with CYP1A2, CYP2C19, CYP2D6 or CYP3A4 activities. Paper-11184960.
Lack of associations among cancer and albumin adducts, ras p21 oncoprotein levels, and CYP1A1, CYP2D6, NAT1, and NAT2 in a nested case-control study of lung cancer within the physicians' health study. Paper-12143150.
A combined analysis with the data of the known tamoxifen predictor CYP2D6 showed an improvement of outcome prediction compared with CYP2D6 or TC21 genotype status alone (per mutated gene HR, 2.35; 95% CI, 1.34-4.14). Paper-13474800.
Conformational restriction of open chain analogs with a more polar tetrahydro-1,3-oxazin-2-one spacer led to the identification of potent urea-based CCR3 antagonists that exhibited excellent selectivity over binding to CYP2D6. Paper-13557018.
This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. Paper-12734479.
Apparent K(m) and V(m) were determined for CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP3A4 and CYP4A11. Paper-12332865.
Thus, women with CYP2D6 EM who smoke have increased susceptibility to high-grade CIN but are less likely to progress to SCC, possibly because they effectively detoxify an unidentified chemical involved in mediating disease progression. Paper-134555.
Advances in the study of autoreactive T cells have occurred mostly in AIH type 2, since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T cells targeting this cytochrome. Paper-12815052.
Inhibition assays demonstrated that tilidine and nortilidine can also inhibit CYP3A4, CYP2C19, CYP2D6, ABCB1, but not ABCG2, whereas inhibition of CYP2D6 and possibly also of CYP3A4 might be clinically relevant. Paper-12969024.
A case-control study on ALL patients and healthy controls in a French-Canadian population was carried out by examining the loci of Phase I, CYP1A1 and CYP2D6, as well as Phase II enzymes, GSTM1, GSTT1, NAT1 and NAT2. Paper-8550443.
CYP2D6 catalyzed desalkyl delavirdine formation was linear with time (up to 30 min) but when catalyzed by cDNA expressed CYP3A4 or human liver microsomes the reaction rate declined progressively with time. Paper-1602212.
Delavirdine, a non-nucleoside inhibitor of HIV-1 reverse transcriptase, is metabolized primarily through desalkylation catalyzed by CYP3A4 and CYP2D6 and by pyridine hydroxylation catalyzed by CYP3A4. Paper-8682011.
The AmpliChip CYP450 Test, which analyzes patient genotypes for cytochrome P450 ( CYP) genes CYP2D6 and CYP2C19, is a major step toward introducing personalized prescribing into the clinical environment. Paper-12124412.
There was strong evidence against linkage for the remaining loci in all families analyzed individually, except for TH, which was uninformative in Families A and B, and CYP2D6, which gave slightly positive pairwise lod scores in Family A. Paper-130907.
CYP2D6 is the rate-limiting enzyme catalyzing the conversion of tamoxifen into metabolites with significantly greater affinity for the ER and greater ability to inhibit cell proliferation. Paper-12673467.
Recombinant CYP microsomes expressing CYP2C9, CYP2C19 and CYP3A4 with co-expressed cytochrome b(5) were used, but those expressing CYP1A2 and CYP2D6 did not have co-expressed cytochrome b(5). Paper-12506248.
These results suggest that CYP2D6 genotype as well as CYP2D6 phenotype are not determinant of susceptibility to systemic lupus erythematosus but the presence of the inactive CYP2D6*4A allele may be a contributory factor. Paper-1575496.
No reduction is seen with plaice CYP1A, despite similar levels of P450 expression and enzyme activity ( ethoxyresorufin O-deethylation) and no inhibition of growth is observed with yeast cells expressing higher levels of human CYP2D6. Paper-839664.
Purified plasma membranes from yeast expressing CYP2D6 sustained NADPH- and cumene hydroperoxide-dependent dextromethorphan demethylation and NADPH- cytochrome c activity confirming previous observations in human hepatocytes. Paper-1501384.
CONCLUSIONS: These findings suggest that the MDR-1 variants are not associated with steady-state plasma concentration of risperidone or 9-hydroxyrisperidone, but CYP2D6 genotypes and age are determinants of these concentrations. Paper-10354435.
Regions previously associated with AS on chromosome 2q (the IL-1 gene cluster) and 22q ( CYP2D6) exhibited nominal linkage in the meta-analysis, providing further statistical support for their involvement in susceptibility to AS. Paper-13197620.
However, the effect became negligible when adrenaline concentration was decreased to 100 microM: whereas a high inhibitory effect was observed in CYP2D6, CYP2C9 and CYP3A4 enzyme activities, the NADPH reductase activity remains unchanged. Paper-13706798.
OBJECTIVE: To determine the effect of 150 mg/day fluvoxamine on the activities of CYP1A2, CYP2D6, CYP3A, N-acetyltransferase-2 ( NAT2), and xanthine oxidase ( XO) by phenotyping with caffeine, dextromethorphan, and midazolam. Paper-1578513.
The contribution of CYP2D6 to the total formation of NAPQI from APAP (1 mM) in human liver was investigated using quinidine (1 microm) as a CYP2D6-specific inhibitor, and varied from 4.5 to 22.4% among 10 livers, with an average at 12.6%. Paper-8512711.
As part of a multicenter prospective observational trial in 176 breast cancer patients, we tested the hypothesis that tamoxifen-induced lipid changes were associated with genetic variants in candidate target genes ( CYP2D6, ESR1, and ESR2). Paper-12787577.
Leucocyte DNA from 118 MS patients and a control group of 200 unrelated healthy individuals was studied for the occurrence of 8 different CYP2D6 allelic variants by using allele-specific PCR amplification, XbaI and EcoRI RFLP analyses. Paper-716018.
The CYP2D6 substrates bufuralol and debrisoquine showed strong inhibition of both tryptophol production from tryptamine in HLM and the formation of indole-3-acetaldehyde from tryptamine catalyzed by recombinant MAO-A. Paper-9707578.
Cytochrome P450 1A2, CYP2A6/7, CYP2D6, CYP3A4/5, and EH mRNAs were approximately one order of magnitude less abundant than CYP2E1 transcripts, with CYP2D6 levels exhibiting the greatest variation (220 fold) between individuals. Paper-1384425.
Cytochrome P450 families CYP1, CYP2 and CYP51 have been investigated for QSAR analysis, including those of CYP2 subfamilies: CYP2A, CYP2B, CYP2C, CYP2D and CYP2E. Paper-9134422.
The combination of a US FDA-approved test, such as the AmpliChip CYP450 Test, and an FDA definition of CYP2D6 as a 'valid biomarker' makes CYP2D6 genotyping a prime candidate to be the first successful pharmacogenetic test in the clinical environment. Paper-12124412.
Judging from the correlation and inhibition studies, NE-125 and NE-152+163mix formations were predominantly mediated by CYP2D6 and NE-098 formation was mediated by multiple CYP forms at a low NE-100 concentration (0.1 microM) in the HLM. Paper-10955140.
Our aim was to study the association between the clinical response to betaxolol in patients with essential hypertension (EH) and polymorphous markers of two genes: beta(1) adrenergic receptor gene ( ADRB1) and cytochrome P450 2D6 gene ( CYP2D6). Paper-13343689.
We genotyped 86 subjects with diagnoses of probable AD to determine if they carried the alpha-1-antichymotrypsin (ACT) A allele, which has been associated with AD, or the CYP2D6 B mutant, found at increased frequency in the Lewy body variant (LBV) of AD. Paper-886949.
CONCLUSION: Our results indicate that TJ-19 at the generally recommended dosage is unlikely to cause pharmacokinetic interaction with co-administered medications primarily dependent on the CYP1A2, CYP2D6, CYP3A, XO, and NAT2 pathways for elimination. Paper-13143855.
In this study, we investigated the effect of genetic polymorphisms in the 5-hydroxytryptamine type 2A, 3A, and 3B ( 5-HT3B) receptors, 5-HT transporter, and CYP2D6 genes on the incidence of paroxetine-induced nausea. Paper-12737041.
However, the lack of a correlation between celecoxib and bufuralol metabolism in hepatic EM or PM microsomes indicates that other CYP subfamilies besides CYP2D may contribute to the polymorphism in canine celecoxib metabolism. Paper-8294612.
Purified CYP2D6 protein with a measured molecular weight of 55772.0 (55769.6 Da predicted) was reconstituted into an active, lipid-vesicle environment with purified rat cytochrome P450 reductase before the addition of substrate and NADPH. Paper-9111593.
BACKGROUND & AIMS: Autoimmune hepatitis type 2 ( AIH-2), a severe juvenile liver disorder of unknown etiology and pathogenesis, is characterized by liver-kidney microsomal antibody type 1 targeting cytochrome P450IID6 ( CYP2D6) and is associated to HLA DRB1*07. Paper-10839022.
To understand the evolutionary sequence of mutational events as well as recently discovered interracial differences, we analyzed the arrangement of the CYP2D haplotype containing a common mutant allele of CYP2D6 associated with a XbaI 44-kb fragment. Paper-75844.
The genetic polymorphism of the CYP2D6 influences plasma concentration of a wide variety of drugs metabolized in the liver by the cytochrome P450 ( CYP) 2D6 enzyme, including antipsychotic drugs used for schizophrenia treatment. Paper-13434893.
MPTP was efficiently oxidized by CYP2D6 to two main products: MPTP-OH (p-hydroxylation) and PTP (N-demethylation), with turnover numbers of 10.09 min(-1) and K(m) of 79.36+/-3 muM (formation of MPTP-OH) and 18.95 min(-1) and K(m) 69.6+/-2.2 muM ( PTP). Paper-12284468.
The purpose of this study was to establish the frequencies of CYP2D6, CYP1A1, GSTM1 and p53 polymorphic genotypes in Tundra Nentsi, which comprises the small group of indigenous people belonging to Northern Mongoloids and Caucasians of Western Siberia. Paper-8646331.
The genes of interest were the dopamine D2 receptor gene ( DRD2), the serotonin 2A and 2C receptor genes ( HTR2A and HTR2C), the P-glycoprotein gene ( ABCB1 or MDR1) and the drug-metabolizing cytochrome P450 2D6 gene ( CYP2D6). Paper-13085529.
After the identification of cytochrome P450 2D6 as the major LKM-1 antigen and cytochrome P450 2C9 as the LKM-2 antigen, family 1 uridine diphosphate-glucuronosyltransferases have been identified as the molecules expressing the major LKM-3 autoepitope. Paper-282930.
METHODS: Up to five single nucleotide polymorphisms ( SNPs) were typed for CYP1A1, CYP1A2, CYP2E1, CYP2D6, EPHX1, MnSOD, AhR, NAT2, CAT, GPX1, PON1, and ADPRT1 by multiplex snapshot single base primer extension method. Paper-11024449.
Genotyping revealed the presence of the frame-shift mutation 138delT only in those subjects who expressed the brain variant CYP2D7, which metabolizes codeine exclusively to morphine unlike hepatic CYP2D6 that metabolizes codeine to nor codeine and morphine. Paper-12253848.
Since in patients with neurofibromatosis type 2, we had observed a significantly increased rate of CYP2D6 mutations leading to PM and apparently predisposing for NF2, we extended our investigation to tumor and peripheral blood samples obtained from NF1 patients. Paper-1349851.
The CYP2D6 crystal structure further validates our homology modeling approach and shows that computational chemistry is a useful and valuable tool to provide models for substrate- bound complexes of CYPs which give insight into CYP-ligand interactions. Paper-12448420.
Autoantibodies against cytochrome P450 2D6 ( CYP2D6), known as anti-liver/kidney microsome type 1 (LKM1) and/or anti-human formiminotransferase cyclodeaminase, formally known as anti-liver cytosol type 1 (LC1) define type 2 autoimmune hepatitis ( AIH). Paper-9446727.
Cross-reactivity due to molecular mimicry at the B-cell level was shown between the CYP2D6 and the HCV NS3 and NS5a proteins and could explain the presence of anti-LKM1 in patients chronically infected with HCV. Paper-11037307.
METHODS: The inhibitory effects of star fruit juice (0.5 to 5%, v/v) against the activities of seven CYP isoforms including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP3A4 and CPR were examined in human liver microsomes. Paper-13451812.
This chapter describes P450 form-selective substrates that can be used to monitor the activities of human P450 enzymes CYP1A, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A, CYP4A11, and CYP7A1. Paper-12016003.
Genotypes in non-tumor tissue were also measured at the cytochrome P450 1A1 ( CYP1A1), cytochrome P450 2D6 ( CYP2D6), glutathione-s-transferase mu ( GSTM), epoxide hydrolase ( EH), and NAD(P)H:quinone oxidoreductase ( NQO1) loci. Paper-781195.
We have investigated the association between the inheritance of the polymorphic cytochrome P-450 2D6 ( CYP2D6) gene and the development of transitional and squamous cell carcinomas ( TCC and SCC) of the bladder in 37 Egyptian cancer patients and 27 matched controls. Paper-12778412.
This treatment also results in increases in NADPH cytochrome P450 reductase and P-glycoprotein (the MDR1 gene product) but has no detectable effect on expression of CYP1A1, CYP2D6, cytochrome b5, liver or intestinal fatty acid binding proteins, or villin. Paper-1011081.
We investigated the association of Parkinson's disease (PD) with two genes encoding liver-detoxifying enzymes, debrisoquine 4-hydroxylase ( CYP2D6) and N-acetyltransferase 2 ( NAT2), and with one gene related to Alzheimer's disease, apolipoprotein E ( APOE). Paper-8584214.
The effects of modified cyclodextrins (CDs) hydroxypropyl-beta-CD and methyl-beta-CD were studied in vitro on cDNA-expressed human cytochrome P-450 ( CYP) activities ( CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Paper-10990108.
The total fraction of the sertindole dose removed by dialysis was less than 0.1% Subjects with B/B genotype (n = 2) for CYP2D6 were associated with a distinctly lower clearance of sertindole ( 6.3 vs 25.3 1.h-1) than subjects with wt/wt genotype for CYP2D6. Paper-1110782.
CONCLUSION: These data indicate a significant influence of the CYP2D6 genotype, minor influence of the CYP2C19 genotype and no influence of the CYP2C9 genotype on plasma concentrations of patients taking mainly second-generation antidepressants. Paper-10529916.
Based on the intrinsic formation clearances and the results of inhibition experiments ( CYP2D6, 50 microM bufuralol; FMO3 mediated, 100 mM methionine) using human liver microsomes, it was estimated that CYP3A contributes to >80% of K11777 metabolite formation. Paper-8654331.
The hHNF4alpha-siRNA also decreased the mRNA levels of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A1, UGT1A9, SULT2A1, ABCB1, ABCB11, ABCC2, OATP1B1 and OCT1, as well as those of PXR and CAR. Paper-13429790.
We determined the molecular and immunohistochemical changes ( p53 gene mutations, p53 protein accumulation and WAF1 protein expression) and genetic polymorphisms of GSTM1, CYP1A1 and CYP2D6 genes in a case series of non-small-cell lung cancers from Silesia. Paper-1927737.
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. Paper-1590065.
To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to rheumatoid arthritis ( RA) and whether CYP2D6 enzyme activity is altered as a result of the disease or its treatment. Paper-133120.
During (but not before) treatment taurine in the CSF correlated with the debrisoquine metabolic ratio (r=-0.93; P=0.0007) Our results might indicate an influence of CYP2D6 on the level of taurine in the CSF that was secondary to the change in plasma cholesterol. Paper-9969034.
CYP enzyme activities were measured by means of the metabolic ratios of sparteine ( CYP2D6), endogenous cortisol metabolism ( CYP3A4), and caffeine ( CYP1A2), as well as by the S/R ratio of mephenytoin ( CYP2C19) and antipyrine clearance. Paper-9204207.
The model performed reasonably well for CYP1A2 and CYP3A4, but poorer predictions were obtained for CYP2D6 and CYP2C because of lack of model complexity and/or inadequate hepatic microsomal activity data to fully describe the maturational process of functional enzyme. Paper-9636119.
Two independent cohorts of 160 and 105 ADHD children treated for 6 weeks with atomoxetine (0.5-1.8 mg/kg per day) were genotyped on CYP2D6, which metabolizes atomoxetine, and 108 single nucleotide polymorphisms in the NET/ SLC6A2 gene. Paper-13913738.
Substrate inhibition assays for five of the major CYP enzymes ( phenacetin for CYP1A2, diclofenac for CYP2C9, (S)-mephenytoin for CYP2C19, dextromethorphan for CYP2D6 and midazolam and testosterone for CYP3A4) in human liver microsomes were developed. Paper-13184840.
The curcuminoid extract inhibited SULT > CYP2C19 > CYP2B6 > UGT > CYP2C9 > CYP3A activities with IC(50) values ranging from 0.99 +/- 0.04 to 25.3 +/- 1.3 microM, whereas CYP2D6, CYP1A2, and CYP2E1 activities were less affected (IC(50) values > 60 microM). Paper-12938472.
Increasing concentrations of the compounds were incubated with a panel of recombinant human CYP isoforms ( CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) and their effects on the conversion of specific surrogate substrates measured fluorometrically in a 96-well plate format. Paper-9216843.
Liver Kidney Microsomal autoantibody type 1(LKM1) directed to cytochrome P4502D6 ( CYP2D6) characterises autoimmune hepatitis type-2 ( AIH-2), but is also found in a proportion of chronic hepatitis C virus (HCV) infected patients, CYP2D6252-271 being a major B- cell autoepitope. Paper-10541742.
Three major groups of cytochrome P450 could be described: a first group of cytochromes P450 expressed in the foetal liver includes the CYP3A7 and 4A1, mostly active on endogenous substrates; a second group (termed early neonatal P450) includes CYP2D6 and 2E1. Paper-1441249.
We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H ( CPH) and 21-hydroxylase ( 21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. Paper-1621886.
Usnic acid was a relatively weak inhibitor of CYP2D6 and a potent inhibitor of CYP2C19 (the concentration eliciting 50% inhibition (IC(50)) = 9 nM) and CYP2C9 (IC(50) = 94 nM), with less potent inhibition of CYP2C8 (IC(50) = 1.9 microM) and CYP2C18 (IC(50) = 6.3 microM). Paper-12743157.
In 26 of the newborns, genotyping analysis was performed for genes functioning in metabolic activation and detoxification ( cytochrome P450 genes: CYP2D6 and CYP1A1, and phase II genes: NAT1, NAT2, GSTT1, GSTM1, GSTP1, and epoxide hydrolase). Paper-2163377.
METHODS: In 187 patients with HNSCC and in 139 healthy control subjects, the polymorphisms of cytochrome P450 1A1 ( CYP1A1), cytochrome P450 2D6 ( CYP2D6), and glutathione S-transferase mu1 and Theta ( GSTM1, GSTT1) were detected by polymerase chain reaction. Paper-9703278.
In the current study, we aimed to estimate the frequencies of 14 polymorphisms in eight genes ( TPMT, NQO1, MTHFR, GSTP1, CYP1A1, CYP2D6, ABCB1, and SLC19A1) in the Singapore multiracial populations by screening 371 cord blood samples from healthy newborns. Paper-12377331.
Gefitinib geometric mean AUCinfinity and peak plasma drug concentration were higher in poor CYP2D6 metabolisers compared with extensive metabolisers (AUCinfinity 3060 vs 1430 ng . h/mL, p < 0.05, ANOVA), although the range of values was wide with considerable overlap between the groups. Paper-12111920.
Concerning the quantitative relations, CYP2D6 exhibited a high affinity with respect to hydroxylation and demethylation (K(m) 0.48-0.74 mumol/l), a high hydroxylation capacity (Vmax 130 mol/hr/ mol CYP) and a somewhat lower demethylation capacity (Vmax 19 mol/ hr/ mol CYP). Paper-1099870.
OBJECTIVE: The goal of this study was to assess the activities of cytochrome P450 ( CYP) 1A2, N-acetyltransferase 2, xanthine oxidase, and CYP2D6 in children with isolated idiopathic GH deficiency before and 3 and 6 months after initiation of r- hGH treatment. Paper-13025600.
Reactivity to microsomal protein and CYP2D6 was significantly (P =.02) associated with LKM1 titers >or=1:320 and was found in 39% of patients, including severe cases and both children (of 4 treated) who achieved a sustained alanine aminotransferase (ALT) normalization after steroid treatment. Paper-9801281.
1. The effects of four individual ginsenosides (Rb1, Rb2, Rc and Rd), two ginkgolides (A and B) and one flavonoid ( quercetin) on CYP2C19-dependent S-mephenytoin 4 cent-hydroxylation and CYP2D6-mediated bufuralol 1 cent-hydroxylation were evaluated in human liver microsomes. Paper-12187386.
In accordance with the elevated formation of the TPT-metabolite in DU-145 cells, the expression of cytochrome P450 ( CYP) isoenzymes CYP3A, CYP2B, CYP2D and CYP2E as measured by Western blot analysis was also higher in this cancer cell line. Paper-1528281.
Fourteen- and 80-fold induction of CYP1A1 and CYP1A2 mRNA were shown, whereas expression of other DMEs was either increased (CYP2C8-2C19, 10-fold; CYP3A5, twofold; FMO1, 2 and 5, twofold; epoxide hydrolase, threefold) or repressed ( CYP2D6 and CYP2E1 to 75% of control values). Paper-10007639.
Inhibition studies using antibodies and characterization of CYP2D6 enzymes expressed in insect cells or human lymphoblastoid cells indicated that the enantioselectivity of PL oxidation, especially the ring 4- and 5-hydroxylations reflected the properties of CYP2D6 in human liver microsomes. Paper-8399367.
These observations have suggested that the CYP17 A2/A2, CYP1B1 Val/Val, and CYP2D6 genotypes may be associated with an altered risk of prostate cancer, while the CYP2D6 and SRD5A2 V89L polymorphism have no association with its risk in the North Indian population. Paper-12014627.
These selective associations are consistent with the hypothesis that an environmental pro-carcinogen fails to be detoxified by CYP3A which may preferentially induce p53 mutations, whereas, an alternative pro-carcinogen that may be activated by CYP2D6, may selectively induce Rb mutations. Paper-558459.
RESULTS: mRNAs of CYP1A1, CYP1B1, and CYP2D6 and of the regulatory factors aryl hydrocarbon receptor ( AHR), aryl hydrocarbon receptor nuclear translocator, and glucocorticoid receptor were expressed in the human nonpigmented ciliary epithelial cell line. Paper-13853696.
RESULTS: Of 15 genetic polymorphisms examined, 5-HT2A 102-T/C, 5-HT2C -759-C/T, 5-HT6 267-C/T, BDNF 66-Val/Met, and CYP2D6 188-C/T significantly influenced body weight, and so did baseline body weight, age, gender, schizophrenia subtype, and treatment duration and efficacy. Paper-11822017.
SNPs in CYP1A1, CYP2A1, CYP2B6, CYP2C, CYP2D6, CYP3A, GSTM1, GSTT1, GSTP1, SULT1A1, SULT1A2, UGT, and MTHFR are associated with breast cancer susceptibility; however, lack of such associations are also reported in some populations. Paper-13031492.
This report describes the time course of CYP2D6 antibodies and the appearance of anti-SMA (without anti-actin, cytokeratin and vimentin reactivity) associated with acute rejection during a 2-year follow-up, in a patient who underwent transplantation at end-stage type 2 autoimmune hepatitis. Paper-8586005.
4. CYP2D6 catalysed O-demethylation with apparent Km and Vmax values of 48.34 +/- 14.48 microM and 5.44 +/- 0.47 pmol min(-1) pmol(-1) CYP, respectively. pHLM catalysed the monitored reaction with an apparent Km = 204.80 +/- 51.81 microM and Vmax = 127.50 +/- 13.25 pmol min(-1) mg(-1) protein. Paper-10531982.
METHODS: The contribution of tramadol (M), O-demethyl tramadol (M1, CYP2D6-mediated) and N-demethyl tramadol (M2, CYP3A4-mediated) to the overall elimination of tramadol and the log M/M2 was assessed in 24-hour urine collections during continuous intravenous tramadol administration. Paper-12216626.
The activities examined were cytochrome P450 ( CYP) isoform activities ( CYP2A6, CYP2D6, CYP2C19, CYP1A2, CYP2E1, CYP3A4 and CYP2C9) and phase 2 conjugation enzyme activities ( phenol sulfotransferase ( PST) and glucuronyl transferase ( UGT)). Paper-9231387.
RESULTS: Comparisons of presupplementation and postsupplementation phenotypic ratio means revealed significant inhibition (approximately 40%) of CYP2D6 (difference, -0.228; 95% confidence interval [CI], -0.268 to -0.188) and CYP3A4/5 (difference, -1.501; 95% CI, -1.840 to -1.163) activity for goldenseal. Paper-11095137.
According to the concept of relative activity factor, it was clarified that CYP2C8 as well as CYP3A4 were significantly involved in amiodarone N-deethylation in human livers at clinically significant concentrations and that the contributions of CYP1A2, CYP2C19, and CYP2D6 were relatively minor. Paper-8654325.
Our results show that, in patients with porphyria and in healthy subjects, exogenous heme is able to accelerate the reactions mediated by the cytochrome isozymes CYP2D6 ( debrisoquin) and CYP3A4 ( lidocaine) but not reactions mediated by CYP1A2 ( caffeine) and CYP2A6 ( coumarin). Paper-8011404.
The porcine enzymes CYP1A, CYP2A and CYP3A all metabolize the same test substrates as the human enzymes, whereas the enzymes CYP2B, CYP2D, and CYP2E in pig on the other hand seem to be different from the human enzymes concerning metabolism of the well know test substrates. Paper-11803325.
We used PCR-RFLP to investigate polymorphism for the most common alleles at two cytochrome-P450 mono-oxygenases ( CYP1A1 and CYP2D6), one NAD[P]H:quinone oxidoreductase ( NQO1), three glutathione S-transferases ( GSTM1, GSTT1, and GSTP1), and one N-acetyltransferase ( NAT2) loci. Paper-1904032.
An elevated proportion of LOH was observed for genotypes at CYP2D6 (17% for the 1/1 and 1/2 genotypes vs 8% for the 2/ 2 genotype), NQO1 (13% for the 1/2 and 2/2 genotypes vs 8% for the 1/1 genotype), and GSTM (15% for the null genotype vs 7% for the wild-type genotype). Paper-781195.
METHODS:In 123 patients, we did PCR analyses of the gene for the multidrug-resistance transporter ( MDR1), which codes for P-glycoprotein, of genes coding for isoenzymes of cytochrome P450, CYP3A4, CYP3A5, CYP2D6, and CYP2C19, and of the gene for the chemokine receptor CCR5. Paper-9191114.
There were significant differences in the steady-state plasma concentrations of risperidone ( ANOVA; p < 0.0001) among the three genotype groups, while the CYP2D6 genotype did not affect the steady-state plasma concentrations of (+)-9-hydroxyrisperidone (p = 0.314) or (-)-9-hydroxyrisperidone (p = 0.957). Paper-9879087.
When comparing the expression change of individual genes with DNA adduct levels, carcinogenic potency or Ah-receptor antagonicity (the last two were taken from literature), several highly correlated genes were found, of which CYP1A1, PRKCA, SLC22A3, NFKB1A, CYP1A2 and CYP2D6 correlated with all parameters. Paper-10823084.
Among 10 kinds of CYP enzymes examined, only CYP2D6 catalyzed p-hydroxylation of the cinnamyl phenyl ring of CZ ( C-2 formation) and FZ (F-2 formation), and only CYP2B6 exhibited activity for p-hydroxylation (C-4 formation) of the diphenylmethyl group of CZ at a substrate concentration of 50 microM. Paper-903514.
Potential genes include MHC (HLA class II, low molecular weight proteasome [LMP], transporter associated with antigen processing (TAP), tumor necrosis factor [TNF]-alpha, and major histocompatibility complex class I chain-related gene A (MICA), as well as non-MHC genes (IL-1RA, IL-6, IL-10, and CYP2D6). Paper-9063388.
Urinary molar ratios of DM to dextrorphan ( MR1) and of DM to methoxymorphinan (MR2) were obtained after a single oral 27.5 mg dose of DM hydrobromide to ten healthy male and four female Caucasians (ten extensive metabolizers (EM) and four poor metabolizers (PM) of DM) to probe activities of CYP2D6 and CYP3A, respectively. Paper-1978564.
Polymorphisms in the selected genes controlling carcinogen metabolism ( CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1, GSTT1) considered separately or in different combinations, were investigated for an association with tobacco smoke-associated squamous cell carcinoma ( SCC) of the larynx. Paper-11286729.
The present study investigated the effect that clinical factors, such as smoking and age, and functional polymorphisms of UGT1A4, CYP1A2, and CYP2D6 genes have on plasma olanzapine concentration, as well as the effects of plasma olanzapine concentrations on Japanese schizophrenic patients' clinical symptoms. Paper-12707828.
METHODS: Three hundred and eighty-four subjects from South Africa (Venda), Tanzania, and Zimbabwe who consented to the study were genotyped for CYP2D6 (CYP2D6*1, *2, *3, *4, *5, and *17) and CYP2C19 (CYP2C19*1, *2, and *3) by PCR-RFLP ( polymerase chain reaction restriction fragment length polymorphism) techniques. Paper-8962829.
This data in the aggregate suggests that the 3 best studied genetic susceptibility factors ( CYP2D6 extensive metabolizers, GST mu null phenotype, and CYP1A1 "mutant" alleles in Asians only) constitute greater risk factors for the more smoking related histologies of lung cancer, but not for adenocarcinoma. Paper-8012804.
In the present study we investigated the prognostic and/or predictive value of functional polymorphisms in cytochrome P450 3A5 CYP3A5 (*3), CYP2D6 (*4), sulphotransferase 1A1 ( SULT1A1; *2) and UDP-glucuronosyltransferase 2B15 ( UGT2B15; *2) in tamoxifen-treated patients with breast cancer. Paper-12477158.
1. The relative roles of human hepatic cytochrome P450 ( CYP) subfamilies participating in ethosuximide metabolism have been studied in vitro using humanized heterologous CYP microsomal systems expressing either CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1 or CYP3A4. Paper-9936248.
In comparison of a panel of 15 recombinant P450 enzymes, they found that in addition to CYP2D6, CYP1A1 is also capable of catalyzing the formation of 4-hydroxylated metabolite of debrisoquine and that the intrinsic clearance of debrisoquine by CYP2D6- mediated 4-hydroxylation is only about twice that by CYP1A1. Paper-9949901.
METHODS: Eighty patients with newly diagnosed with breast cancer who were beginning tamoxifen therapy (20 mg/day orally), 24 of whom were taking CYP2D6 inhibitors, were genotyped for common alleles of the CYP2D6, CYP2C9, CYP3A5, and sulfotransferase ( SULT) 1A1 genes. Paper-11455901.
This approach is illustrated with the prediction of hERG channel blocking and cytochrome P450 2D6 inhibition, where combination of two predictive models (with >80% of compounds correctly predicted) resulted in models with even better predictive values (with >90% of compounds correctly predicted for those classes of interest). Paper-10790809.
AIMS: The purpose of this research was to characterize CYP2D6, GST-M1 and GST- T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end-stage renal disease. Paper-9818476.
This article focuses on opioid use for pain management, their risks of toxicity and addiction, adverse reactions, undertreatment for fear of addiction, and integration of novel diagnostics, such as the pharmacogenetic biomarkers CYP2D6 and OPRM1 as holding promise for assessing a patient's risk of adverse events or likelihood of efficacy. Paper-13485110.
The 1,2,3,6-tetrahydropyridine scaffold was chosen due to its common occurrence in the structures of CYP2D6 ligands such as the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the dehydrated haloperidol metabolite N-[4-(4-fluorophenyl)-4-oxobutyl]-4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine ( HPTP). Paper-10020332.
An additional blood sample was obtained from this individual to determine if he possessed any of the known CYP2C9 or CYP2C19 allelic variants that would account for his poor clearance of the CYP2C9 substrates ( phenytoin and glipizide) compared with the CYP3A4 ( nifedipine) and CYP2D6 ( chlorpheniramine) substrates. Paper-1843017.
Thirty-eight stable OLTx patients, separated into younger and older age groups, and 21 healthy subjects were given a 5-drug cocktail including chlorzoxazone ( CYP2E1), caffeine ( CYP1A2), dapsone ( CYP3A4), mephenytoin ( CYP2C19), and debrisoquin ( CYP2D6). Paper-11525104.
To date the only genetic assays that are available as FDA-approved in vitro diagnostic ( IVD) kits are for analysis of the Factor V (Leiden) and Factor II (promoter G to A) mutations associated with thrombophilia risk for assessment of cytochrome P450 2D6 and 2C19 polymorphisms and for analysis of mutations in the CFTR gene. Paper-12367043.
Tipranavir is metabolized by cytochrome P450 ( CYP) 3A and, when combined with ritonavir in vitro, causes inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A in addition to induction of glucuronidase and the drug transporter P-glycoprotein. Paper-13263300.
Of the enzymes investigated, CYP1A2, CYP3A4, CYP2D6, CYP2C8, CYP2C19 and, to a lesser extent, CYP2C9-cys, CYP2C9-arg and CYP3A5 were apparently involved in N-demethylation, while CYP1A2, CYP3A4, FMO3 and, to a lesser extent, CYP2C8, CYP2C19 and CYP3A5 were found to catalyse the formation of clozapine N-oxide. Paper-1705470.
METHODS: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. Paper-11517886.
The accumulation of CYP2D6 and CYP2E1 proteins, which are constitutively expressed in confluent cultures, and the production of fibrinogen and apolipoprotein (Apo) B100 exhibited similar behavior, while nicotinamide adenine dinucleotide phosphate cytochrome c reductase activity was affected neither by cell density nor by EGF. Paper-998990.
The highest impact is seen for drugs with a narrow therapeutic index, with important examples emerging from treatment with antidepressants, oral anticoagulants, and cytostatics, which are metabolised by the polymorphic enzymes cytochrome P450 2D6 ( CYP2D6), cytochrome P450 2C9 ( CYP2C9), and thiopurine-S-methyltransferase ( TPMT), respectively. Paper-9708464.
The substrate structure-activity relationships described for the major human drug-metabolizing cytochrome P450 ( P450 or CYP) enzymes suggest that the H1 receptor antagonist terfenadine could interact with CYP2D6 either as a substrate or as an inhibitor, in addition to its known ability to act as a substrate for CYP3A4. Paper-1613700.
The activities of hepatic cytochrome P450 ( CYP) 1A2, N-acetyltransferase 2 ( NAT-2), xanthine oxidase ( XO), and CYP2D6 were evaluated in 12 young children (aged 3-8 years) with mild cystic fibrosis ( CF) and 12 age-matched healthy control subjects by use of standard caffeine and dextromethorphan phenotyping methods. Paper-10210291.
In order to evaluate whether the debrisoquine hydroxylation seen in subjects with this haplotype is catalysed by a functionally similar enzyme to CYP2D6 or is catalysed by another type of P450 isozyme, product selectivity of the 4-hydroxylation was studied in 27 Chinese. The inhibition of CYP2D6 by quinidine was also investigated. Paper-93525.
Metabolic enzymes involved in benzene activation or detoxification, including cytochrome P-450 1A1 ( CYP1A1), cytochrome P-450 2D6 ( CYP2D6), UDP-glucuronosyltransferase 1A6 ( UGT1A6), UDP-glucuronosyltransferase1A7 ( UGT1A7), and sulfotransferase 1A1 ( SULT1A1), were studied for their roles in human susceptibility to benzene poisoning. Paper-13221332.
This study was conducted to examine the involvement of cytochrome P450 ( CYP450) and the flavin-containing monooxygenase ( FMO) in the sulphoxidation of ethyl methyl sulphide ( EMS), 4-chlorophenyl methyl sulphide (CPMS) and diphenyl sulphide (DPS) in human liver microsomes from a phenotypic CYP2D6 extensive metabolizer. Paper-9705111.
In a metabolic enzyme characterization study using P450-expressing insect cell microsomes, beraprost (BP) was slightly metabolized in the presence of CYP2C8, but not metabolized by the other P450 isoforms ( CYP1A1, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP4A11) at a concentration of 20 microM. Paper-13017709.
1. Linkage analysis, using locus-specific primers, showed a maximum sex-average lod score of 8.12 ( theta = 0.00) between the marker pH130 (D22S64) and CYP2D6, of 6.92 ( theta = 0.00) between the marker KI839 (D22S95) and CYP2D6, and of 4.80 ( theta = 0.036) between the platelet-derived growth factor beta subunit gene (PDGFB) and CYP2D6. Paper-7706027.
These include a polymorphism in the CYP2D6 gene, encoding a cytochrome p450 family member involved in phase I drug metabolism, and polymorphisms in genes encoding enzymes involved in phase II drug metabolism, including N-acetyltransferase ( NAT2), catechol-O-methyltransferase ( COMT), and phenol sulfotransferase ( P-PST, SULT1A1). Paper-10453087.
OBJECTIVE: To test the hypotheses that (1) CYP2D6 genotype is associated with pharmacokinetics of ophthalmic timolol and (2) variation in genotypes of ADRB1 (beta(1)-adrenoceptor) and GNAS1 (alpha-subunit of G-protein) modulate heart rate (HR), and systolic (SAP) and diastolic (DAP) arterial pressure responses to timolol. Paper-11485189.
We determined whether the multiple cluster MPP was associated with characteristics associated with sensitivity to UV or glutathione S-transferase (GST) GSTT1, GSTM1, cytochrome P450 ( CYP) CYP2D6, tumour necrosis factor (TNF)-alpha and vitamin D receptor ( VDR) genotypes previously associated with BCC presentational phenotypes. Paper-8777288.
Lu 25-109 was metabolized by human liver microsomes to Lu 31-126 (de-ethyl Lu 25-109) mainly by CYP2D6; to Lu 29-297 [3-(2-ethyltetrazol-5-yl)-1-methyl-pyridinium] and Lu 25-077 ( demethyl Lu 25-109) mainly by CYP1A2, CYP2A6, CYP2C19, and CYP3A4; and to Lu 32-181 ( Lu 25-109 N-oxide) by CYP1A2 and possibly by CYP2C19. Paper-1736698.
The relative influence of NQO1 null was studied in a multivariate model that included: (i) 241 patients in whom GSTM1 B, GSTT1 null and CYP2D6 EM genotype data were available, and (ii) 101 patients in whom these genotypes, as well as data on GSTM3, CYP1A1 and melanocyte-stimulating hormone receptor ( MC1R) genotypes were available. Paper-1944359.
The genes with functional polymorphisms that are reported here for the first time include AGTRL2, CAT, CHRNA5, CTSG, CYP2D6, DLD, ERCC1, GABRA1, GABRP, HNRPH3, HIP1, IGKV1-9, KCNJ15, KCNK6, KLK1, MSMB, MYOC, NPY2R, NOTCH4, ORM2, PEDF, PTPRCAP, ST16 ( IL24), SULT1A1, and TSHR. Paper-11539918.
The aim of this study was to explore the frequencies of polymorphisms in drug-metabolizing enzymes ( CYP1A1, CYP2C9, CYP2C19, CYP3A4, CYP2D6, CYP3A5, DPYD, UGT1A1, GSTM1, GSTP1, GSTT1) and drug transporters (ABCB1[MDR1] and ABCC2[MRP2]), and to investigate the LD and perform haplotype analysis of these polymorphisms in a Dutch population. Paper-12124415.
Using P450 isoform-selective inhibitors and recombinant heterologously expressed enzymes, it was demonstrated that several P450 enzymes catalyzed sertraline N-demethylation, with CYP2B6 contributing the greatest extent, and lesser contributions from CYP2C19, CYP2C9, CYP3A4, and CYP2D6. Paper-11118674.
OBJECTIVES: To determine whether patients with idiopathic systemic lupus erythematosus ( SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 genotypes and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clinical features of SLE. Paper-1884197.
OBJECTIVE: Our objective was to explore the relationships between imatinib pharmacokinetics and 9 allelic variants in 7 genes coding for adenosine triphosphate-binding cassette transporters ( ABCB1 and ABCG2) and enzymes ( cytochrome P450 [ CYP] 2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) of putative relevance for imatinib. Paper-12079957.
These synonyms are used for gene CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6): P450-DB1, P450DB1, P450C2D, MGC120390, MGC120389, Debrisoquine 4-hydroxylase, Cytochrome P450 2D6, CYPIID6, CYP2DL1, CYP2D@, CYP2D, CPD6.
These accession numbers are used for gene CYP2D6: Q59FG8 (UNIPROT__AC), Q2XND6 (UNIPROT__AC), M24499 (NCBI_GENBANK__AC), AK309600 (NCBI_GENBANK__AC).
CYP2D6 is a homologue of CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) from Pan troglodytes.
CYP2D6 is a homologue of Cyp2d4v1 (cytochrome P450, family 2, subfamily d, polypeptide 4) from Rattus norvegicus.
CYP2D6 is a homologue of Cyp2d22 (cytochrome P450, family 2, subfamily d, polypeptide 22) from Mus musculus.
CYP2D6 is a homologue of CYP2D15 (cytochrome P450 2D) from Canis lupus familiaris.
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