R F Tyndale

Summary

Affiliation: University of Toronto
Country: Canada

Publications

  1. ncbi CYP2A6 genetic variation and potential consequences
    Chun Xu
    Centre for Addiction and Mental Health, University of Toronto, Toronto M5S 1A8, Canada
    Adv Drug Deliv Rev 54:1245-56. 2002
  2. ncbi Characterization of the novel CYP2A6*21 allele using in vivo nicotine kinetics
    Nael Al Koudsi
    Centre for Addiction and Mental Health, and Department of Pharmacology, University of Toronto, Toronto, ON, Canada
    Eur J Clin Pharmacol 62:481-4. 2006
  3. ncbi CYP2A6 genotype, phenotype, and the use of nicotine metabolites as biomarkers during ad libitum smoking
    Viba Malaiyandi
    Department of Pharmacology, Center for Addiction and Mental Health, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Cancer Epidemiol Biomarkers Prev 15:1812-9. 2006
  4. pmc Pharmacogenetics: a tool for identifying genetic factors in drug dependence and response to treatment
    Margaret Mroziewicz
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada
    Addict Sci Clin Pract 5:17-29. 2010
  5. pmc Variation in trans-3'-hydroxycotinine glucuronidation does not alter the nicotine metabolite ratio or nicotine intake
    Andy Z X Zhu
    Department Pharmacology and Toxicology, University of Toronto, Ontario, Canada
    PLoS ONE 8:e70938. 2013
  6. doi Nicotine kinetics in zebra finches in vivo and in vitro
    Sharon Miksys
    Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Departments of Pharmacology and Toxicology and Psychiatry, University of Toronto, Toronto, Canada
    Drug Metab Dispos 41:1240-6. 2013
  7. pmc Pilot Study of CYP2B6 Genetic Variation to Explore the Contribution of Nitrosamine Activation to Lung Carcinogenesis
    Catherine A Wassenaar
    Department of Pharmacology and Toxicology, The University of Toronto, Toronto, ON M5S 1A8, Canada
    Int J Mol Sci 14:8381-92. 2013
  8. pmc The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex
    Andy Z X Zhu
    Departments of Psychiatry, Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    Cancer Epidemiol Biomarkers Prev 22:708-18. 2013
  9. pmc Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data
    Lisa Sanderson Cox
    Department of Preventive Medicine and Public Health, University of Kansas Medical Center, Kansas City, KS, USA
    Trials 12:22. 2011
  10. ncbi Genetics of alcohol and tobacco use in humans
    Rachel F Tyndale
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Ann Med 35:94-121. 2003

Collaborators

Detail Information

Publications111 found, 100 shown here

  1. ncbi CYP2A6 genetic variation and potential consequences
    Chun Xu
    Centre for Addiction and Mental Health, University of Toronto, Toronto M5S 1A8, Canada
    Adv Drug Deliv Rev 54:1245-56. 2002
    ....
  2. ncbi Characterization of the novel CYP2A6*21 allele using in vivo nicotine kinetics
    Nael Al Koudsi
    Centre for Addiction and Mental Health, and Department of Pharmacology, University of Toronto, Toronto, ON, Canada
    Eur J Clin Pharmacol 62:481-4. 2006
    ..The impact of CYP2A6*21 (K476R) on in vivo nicotine metabolism and disposition was investigated...
  3. ncbi CYP2A6 genotype, phenotype, and the use of nicotine metabolites as biomarkers during ad libitum smoking
    Viba Malaiyandi
    Department of Pharmacology, Center for Addiction and Mental Health, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Cancer Epidemiol Biomarkers Prev 15:1812-9. 2006
    ....
  4. pmc Pharmacogenetics: a tool for identifying genetic factors in drug dependence and response to treatment
    Margaret Mroziewicz
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada
    Addict Sci Clin Pract 5:17-29. 2010
    ..Pharmacogenetics can inform medication development and personalized treatment strategies; challenges lie along the pathway to its general use in clinical practice...
  5. pmc Variation in trans-3'-hydroxycotinine glucuronidation does not alter the nicotine metabolite ratio or nicotine intake
    Andy Z X Zhu
    Department Pharmacology and Toxicology, University of Toronto, Ontario, Canada
    PLoS ONE 8:e70938. 2013
    ..We investigated whether slower 3HC glucuronidation alters NMR, altering its ability to predict CYP2A6 activity and reducing its clinical utility...
  6. doi Nicotine kinetics in zebra finches in vivo and in vitro
    Sharon Miksys
    Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Departments of Pharmacology and Toxicology and Psychiatry, University of Toronto, Toronto, Canada
    Drug Metab Dispos 41:1240-6. 2013
    ..52; P = 0.04) and bupropion metabolism (r = 0.81; P < 0.001), suggesting CYP2B-mediation of nicotine metabolism as seen in rats. These results will facilitate further investigation of nicotine's effects in zebra finches...
  7. pmc Pilot Study of CYP2B6 Genetic Variation to Explore the Contribution of Nitrosamine Activation to Lung Carcinogenesis
    Catherine A Wassenaar
    Department of Pharmacology and Toxicology, The University of Toronto, Toronto, ON M5S 1A8, Canada
    Int J Mol Sci 14:8381-92. 2013
    ..0 high-risk genotypes, respectively. Findings from this pilot point to genetic variation in CYP2B6 as a lung cancer risk factor supporting a role for nitrosamine metabolic activation in the molecular mechanism of lung carcinogenesis...
  8. pmc The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex
    Andy Z X Zhu
    Departments of Psychiatry, Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    Cancer Epidemiol Biomarkers Prev 22:708-18. 2013
    ..However, a given cotinine level may not represent the same tobacco exposure; for example, African-Americans have higher cotinine levels than Caucasians after controlling for exposure...
  9. pmc Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data
    Lisa Sanderson Cox
    Department of Preventive Medicine and Public Health, University of Kansas Medical Center, Kansas City, KS, USA
    Trials 12:22. 2011
    ..This paper describes the study design, measures, and baseline characteristics from Kick It at Swope III (KIS-III), the first treatment study of bupropion for African American light smokers...
  10. ncbi Genetics of alcohol and tobacco use in humans
    Rachel F Tyndale
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Ann Med 35:94-121. 2003
    ..In addition, each section will review briefly some of the confounding issues in the specific type of approach utilized...
  11. ncbi Differences in propensity for drinking alcohol are reflected in subunit- and region-specific GABA(A) receptor levels
    R F Tyndale
    Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Canada
    Addict Biol 4:309-16. 1999
    ..005 versus HES rats 0.610 +/- 0.006, p=0.03). These data suggest that the differences in GABA receptors were due either to the different propensities of the groups to consume ethanol or were caused by their differing ethanol exposure...
  12. ncbi Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence
    R F Tyndale
    Addiction Research Foundation, Women s College Hospital, Toronto, Ontario, Canada
    Pharmacogenetics 7:375-9. 1997
    ....
  13. ncbi Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior
    Rachel F Tyndale
    Center for Addictions and Mental Health, Toronto, Canada
    Ther Drug Monit 24:163-71. 2002
    ....
  14. ncbi A common genetic defect in nicotine metabolism decreases risk for dependence and lowers cigarette consumption
    R F Tyndale
    Centre for Addictions and Mental Health, Toronto, Ontario, Canada
    Nicotine Tob Res 1:S63-7; discussion S69-70. 1999
    ..In addition we need to gain a better understanding of how manipulating this enzyme could be used therapeutically in prevention and treatment of smoking as well as in exposure reduction...
  15. ncbi Pentobarbital decreases the gamma-aminobutyric acidA receptor subunit gamma-2 long/short mRNA ratio by a mechanism distinct from receptor occupation
    R F Tyndale
    Addiction Research Foundation and Department of Pharmacology, University of Toronto, Canada
    J Pharmacol Exp Ther 283:350-7. 1997
    ..Furthermore, the changes in the gamma-2L/S ratio produced by pentobarbital exposure may have significant effects on the function of an important brain protein, the GABA(A) receptor...
  16. ncbi Characterization of cytochrome P-450 2D1 activity in rat brain: high-affinity kinetics for dextromethorphan
    R F Tyndale
    Centre for Addiction and Mental Health and Departments of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Drug Metab Dispos 27:924-30. 1999
    ....
  17. ncbi Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk
    R F Tyndale
    Centre for Addictions and Mental Health, Toronto, Ontario, Canada
    Drug Metab Dispos 29:548-52. 2001
    ..Both kinetic and behavioral experiments in human smokers demonstrated that inhibiting CYP2A6 in vivo decreased nicotine metabolism and smoking behavior. This article summarizes the preliminary results from our studies...
  18. ncbi An in vivo pilot study characterizing the new CYP2A6*7, *8, and *10 alleles
    C Xu
    Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Biochem Biophys Res Commun 290:318-24. 2002
    ....
  19. ncbi Inhibition of cytochrome P450 2A6 increases nicotine's oral bioavailability and decreases smoking
    E M Sellers
    Department of Pharmacology, Centre for Research in Women s Health, University of Toronto, Ontario, Canada
    Clin Pharmacol Ther 68:35-43. 2000
    ..Hepatic CYP2A6 accounts for nicotine's low systemic bioavailability, precluding oral nicotine replacement to treat dependence...
  20. pmc Identification of novel CYP2A6*1B variants: the CYP2A6*1B allele is associated with faster in vivo nicotine metabolism
    J C Mwenifumbo
    Department of Pharmacology, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    Clin Pharmacol Ther 83:115-21. 2008
    ..1, 34.2+/-12.3, and 41.3+/-11.3, P<0.001) excreted in the urine. We report evidence that CYP2A6*1B genotype is associated with faster nicotine clearance in vivo, which will be important to future CYP2A6 genotype association studies...
  21. ncbi Flunitrazepam metabolism by cytochrome P450S 2C19 and 3A4
    T Kilicarslan
    Department of Pharmacology, University of Toronto, Toronto, Canada
    Drug Metab Dispos 29:460-5. 2001
    ..03 microM). We conclude that the polymorphic enzyme CYP2C19 importantly mediates flunitrazepam demethylation, which may alter the efficacy and safety of the drug, while CYP3A4 catalyzes the formation of 3-hydroxyflunitrazepam...
  22. pmc Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers
    M K Ho
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    Clin Pharmacol Ther 85:635-43. 2009
    ..61, 95% CI 0.95-2.72, P = 0.08). The determination of the 3HC/COT ratio, and possibly CYP2A6 genotype, may be useful in the future for personalizing the choice of smoking cessation treatment in African-American light smokers...
  23. ncbi Overview of the pharmacogenomics of cigarette smoking
    M K Ho
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Canada
    Pharmacogenomics J 7:81-98. 2007
    ..This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation...
  24. doi Differential effects of nicotine treatment and ethanol self-administration on CYP2A6, CYP2B6 and nicotine pharmacokinetics in African green monkeys
    C S Ferguson
    Centre for Addiction and Mental Health and Departments of Psychiatry, Pharmacology, and Toxicology, University of Toronto, Toronto, Canada
    J Pharmacol Exp Ther 343:628-37. 2012
    ..In vivo nicotine pharmacokinetics are differentially affected by ethanol and nicotine, but when both drugs are used in combination the effect more closely resembles ethanol alone...
  25. ncbi Low doses of nicotine and ethanol induce CYP2E1 and chlorzoxazone metabolism in rat liver
    L A Howard
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    J Pharmacol Exp Ther 299:542-50. 2001
    ..g., smokers, patients with Alzheimer's disease, ulcerative colitis, neuropsychiatric motor disorders)...
  26. pmc CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion
    A Z X Zhu
    Center for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    Clin Pharmacol Ther 92:771-7. 2012
    ..These findings suggest that dosing of bupropion to achieve a hydroxybupropion level of 0.7 μg/ml or increasing bupropion dose for CYP2B6 slow metabolizers could improve bupropion's cessation outcomes...
  27. ncbi Mimicking gene defects to treat drug dependence
    E M Sellers
    Department of Pharmacology, University of Toronto, Ontario, Canada
    Ann N Y Acad Sci 909:233-46. 2000
    ..Inhibiting CYP2A6 (e.g. tranylcypromine, methoxsalen) decreases smoking and the activation of procarcinogens. By mimicking these gene defects the risk of dependence can be decreased in individuals and new treatments developed...
  28. ncbi CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial
    Anna M Lee
    Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, 1 King s College Circle Toronto, Ontario, Canada
    Biol Psychiatry 62:635-41. 2007
    ..Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome...
  29. ncbi Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro
    W Zhang
    Department of Pharmacology, University of Toronto, Toronto, Canada
    Drug Metab Dispos 29:897-902. 2001
    ....
  30. ncbi Cytochrome P450 2D6 and treatment of codeine dependence
    M K Romach
    Department of Psychiatry, Centre for Research in Women s Health, University of Toronto, Ontario, Canada
    J Clin Psychopharmacol 20:43-5. 2000
    ..Opiate use decreased by 30% to 100% of baseline use (p < 0.0001) in parallel with a decrease in CYP2D6 activity. Fluoxetine may have a role in the treatment of opiate dependence by decreasing opiate-reinforcing properties...
  31. ncbi Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy
    V Malaiyandi
    Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, ON, Canada
    Mol Psychiatry 11:400-9. 2006
    ..5+/-8.0, respectively, P<0.02). These findings indicate that CYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, NRT...
  32. ncbi Induction of CYP2B1/2 and nicotine metabolism by ethanol in rat liver but not rat brain
    K A Schoedel
    Department of Pharmacology, University of Toronto, 1 King's College Circle, M5S 1A8, Toronto, Ontario, Canada
    Biochem Pharmacol 62:1025-36. 2001
    ....
  33. ncbi Hepatic CYP2B6 is altered by genetic, physiologic, and environmental factors but plays little role in nicotine metabolism
    N Al Koudsi
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
    Xenobiotica 40:381-92. 2010
    ..CYP2B6*6 was not associated with different nicotine kinetics. In summary, CYP2B6 protein expression was associated with genotype, gender, and exposure to inducers, but not with nicotine C-oxidation activity...
  34. ncbi Interactions between age and the aversive effects of nicotine withdrawal under mecamylamine-precipitated and spontaneous conditions in male Wistar rats
    Megan J Shram
    Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, T700, Toronto, ON, Canada M5S 2S1
    Psychopharmacology (Berl) 198:181-90. 2008
    ..Although adolescents may exhibit a greater susceptibility to nicotine addiction, relatively little is known about the influence of the aversive effects of nicotine withdrawal in maintaining smoking behavior...
  35. ncbi Induction and recovery time course of rat brain CYP2E1 after nicotine treatment
    Meenal Joshi
    Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Drug Metab Dispos 34:647-52. 2006
    ..Those affected may include current and passive smokers and people that may be treated with nicotine such as smokers and, potentially, patients with Alzheimer's, Parkinson's disease, or ulcerative colitis...
  36. ncbi Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians
    Kerri A Schoedel
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Pharmacogenetics 14:615-26. 2004
    ..Slow inactivators also smoked fewer cigarettes per day and had an earlier age of first smoking (only dependent smokers)...
  37. ncbi Nicotine self-administration in mice is associated with rates of nicotine inactivation by CYP2A5
    Eric C K Siu
    Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, Canada
    Psychopharmacology (Berl) 184:401-8. 2006
    ..Different mouse strains self-administer different amounts of oral nicotine and quantitative trait loci analyses in mice suggested that Cyp2a5 may be involved in differential nicotine consumption behaviors...
  38. pmc Association of CHRNA5-A3-B4 SNP rs2036527 With Smoking Cessation Therapy Response in African-American Smokers
    A Z X Zhu
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    Clin Pharmacol Ther 96:256-65. 2014
    ..Together, our data suggest that among African Americans, CHRNA5-A3-B4 variants are not associated with baseline smoking but can influence smoking abstinence during active pharmacotherapy. ..
  39. ncbi The role of cytochrome P450 2C19 activity in flunitrazepam metabolism in vivo
    I Gafni
    Institute of Medical Science, dagger Faculty of Pharmacy, double dagger Department of Pharmacology and section sign University of Toronto, Toronto, Canada
    J Clin Psychopharmacol 23:169-75. 2003
    ....
  40. pmc Utility and relationships of biomarkers of smoking in African-American light smokers
    Man Ki Ho
    Centre for Addiction and Mental Health and Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada
    Cancer Epidemiol Biomarkers Prev 18:3426-34. 2009
    ....
  41. ncbi CYP2B6 is expressed in African Green monkey brain and is induced by chronic nicotine treatment
    Anna M Lee
    Department of Pharmacology, Centre for Addiction and Mental Health, University of Toronto, 1 King s College Circle, Ontario, Canada
    Neuropharmacology 50:441-50. 2006
    ..In conclusion, CYP2B6 protein is expressed in specific cells in monkey brain and is induced by chronic nicotine treatment which may impact central metabolism of CYP2B6 substrates such as bupropion and nicotine...
  42. ncbi Genotyping human CYP2A6 variants
    Shari D Goodz
    Center for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto MSS 1A8, Canada
    Methods Enzymol 357:59-69. 2002
  43. ncbi Ethnic variation in CYP2A6*7, CYP2A6*8 and CYP2A6*10 as assessed with a novel haplotyping method
    Jill C Mwenifumbo
    University of Toronto, Toronto, Canada
    Pharmacogenet Genomics 15:189-92. 2005
    ..Our new method demonstrated higher frequencies of CYP2A6*7 and CYP2A6*10, and a lower frequency of CYP2A6*8 in Asian populations, but no significant change of allele frequencies in Caucasian or African-Canadian populations...
  44. ncbi Down-regulation of hepatic nicotine metabolism and a CYP2A6-like enzyme in African green monkeys after long-term nicotine administration
    Kerri A Schoedel
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Mol Pharmacol 63:96-104. 2003
    ..Consistent with the slower nicotine metabolism observed in smokers, nicotine may decrease its own metabolism in primates by decreasing the expression of the primary nicotine-metabolizing enzyme CYP2A6...
  45. ncbi Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence
    Viba Malaiyandi
    Department of Pharmacology and Medicine, 1 King s College Circle, University of Toronto, Canada M5S 1A8
    Clin Pharmacol Ther 77:145-58. 2005
    ..Implications of these recent findings on current and novel treatment approaches for smoking cessation and tobacco-related lung cancer will also be discussed...
  46. ncbi Induction of nicotine-metabolizing CYP2B1 by ethanol and ethanol-metabolizing CYP2E1 by nicotine: summary and implications
    Kerri A Schoedel
    Department of Pharmacology, University of Toronto, Ontario, M5S 1A8, Toronto, Canada
    Biochim Biophys Acta 1619:283-90. 2003
    ..Other implications, such as altered pharmacology and toxicology of drugs metabolized by these enzymes, as well as changes in pro-carcinogen and pro-toxin activation are also discussed...
  47. ncbi Rat hepatic CYP2E1 is induced by very low nicotine doses: an investigation of induction, time course, dose response, and mechanism
    Alina L Micu
    Department of Pharmacology, University of Toronto, Canada
    J Pharmacol Exp Ther 306:941-7. 2003
    ..g., smokers, patients with Alzheimer's disease, ulcerative colitis or Parkinson's disease)...
  48. pmc New CYP2A6 gene deletion and conversion variants in a population of Black African descent
    Jill C Mwenifumbo
    Department of Pharmacology, Room 4326 Medical Sciences Building, 1 King s College Circle, CAMH and University of Toronto, Toronto, ON M5S 1A8, Canada
    Pharmacogenomics 11:189-98. 2010
    ..Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing nicotine and nitrosamine precarcinogens. Our aim was to discover and characterize new CYP2A6 alleles in a population of Black African descent...
  49. doi Hepatic CYP2A6 levels and nicotine metabolism: impact of genetic, physiological, environmental, and epigenetic factors
    Nael Al Koudsi
    Department of Pharmacology and Toxicology, University of Toronto, ON, Canada
    Eur J Clin Pharmacol 66:239-51. 2010
    ..We investigated the role of genetic, physiological, environmental, and epigenetic factors in regulating CYP2A6 expression and nicotine metabolism...
  50. pmc Chronic nicotine treatment induces rat CYP2D in the brain but not in the liver: an investigation of induction and time course
    Jiang Yue
    The Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    J Psychiatry Neurosci 33:54-63. 2008
    ..The aims of this study were to investigate whether nicotine can induce rat brain CYP2D, to determine the recovery time course of the induction and to investigate the mechanism of induction through measuring mRNA levels over time...
  51. ncbi Decreasing smoking behaviour and risk through CYP2A6 inhibition
    Edward M Sellers
    Department of Pharmacology, Psychiatry, Medicine University of Toronto, Ontario M5T 3A9, Toronto, Canada
    Drug Discov Today 8:487-93. 2003
    ..Further, we discuss a range of models for proof-of-concept studies for new treatments to alleviate tobacco dependence..
  52. doi Brain drug-metabolizing cytochrome P450 enzymes are active in vivo, demonstrated by mechanism-based enzyme inhibition
    Sharon Miksys
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, ON, Canada
    Neuropsychopharmacology 34:634-40. 2009
    ..Selective induction of metabolically active drug metabolizing enzymes in the brain may also provide ways to control prodrug activation in specific brain regions as a novel therapeutic avenue...
  53. ncbi Characterization and comparison of nicotine and cotinine metabolism in vitro and in vivo in DBA/2 and C57BL/6 mice
    Eric C K Siu
    The Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada
    Mol Pharmacol 71:826-34. 2007
    ..Genetic differences in Cyp2a5 potentially contributed to similar nicotine but different cotinine metabolism, which may confound the interpretation of nicotine pharmacological studies and studies using cotinine as a biomarker...
  54. ncbi Genetic variability in CYP2A6 and the pharmacokinetics of nicotine
    Jill C Mwenifumbo
    University of Toronto, Toronto, Ontario, M5S 1A8, Canada
    Pharmacogenomics 8:1385-402. 2007
    ..Furthering knowledge in this area will improve interpretation of studies examining smoking behavior, as well as those using nicotine as a therapeutic agent...
  55. ncbi Nicotine metabolism and CYP2A6 activity in a population of black African descent: impact of gender and light smoking
    Jill C Mwenifumbo
    The Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Canada M5S 1A8
    Drug Alcohol Depend 89:24-33. 2007
    ..005). These findings highlight the need for smoking status and gender to be considered when interpreting studies using nicotine...
  56. ncbi Non-nicotinic therapies for smoking cessation
    Eric C K Siu
    Center for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, Canada
    Annu Rev Pharmacol Toxicol 47:541-64. 2007
    ..In conclusion, promising new therapeutic products are emerging and they will provide smokers additional options to assist in achieving smoking cessation...
  57. ncbi CYP2B6 genotype does not alter nicotine metabolism, plasma levels, or abstinence with nicotine replacement therapy
    Anna M Lee
    The Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Cancer Epidemiol Biomarkers Prev 16:1312-4. 2007
  58. pmc A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent
    Man Ki Ho
    Department of Pharmacology, Centre for Addiction and Mental Health, University of Toronto, Ontario, Toronto, Canada
    Pharmacogenet Genomics 18:67-75. 2008
    ..We have identified a novel allele, CYP2A6*23 (2161C>T, R203C), in individuals of Black-African descent and investigated its impact on enzyme activity and association with smoking status...
  59. ncbi Drugs and genotypes: how pharmacogenetic information could improve smoking cessation treatment
    Anna M Lee
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Canada
    J Psychopharmacol 20:7-14. 2006
    ..This review will highlight examples of how pharmacogenetic information from central and peripheral candidate genes could contribute to improving smoking cessation outcomes by these two approaches...
  60. ncbi In vivo and in vitro characterization of chlorzoxazone metabolism and hepatic CYP2E1 levels in African Green monkeys: induction by chronic nicotine treatment
    Anna M Lee
    The Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada
    Drug Metab Dispos 34:1508-15. 2006
    ..Thus, nicotine exposure may affect the metabolism of CYP2E1 substrates such as acetaminophen, ethanol, and benzene...
  61. ncbi Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics
    Sharon Miksys
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Canada
    J Neurochem 82:1376-87. 2002
    ..These data suggest that in alcoholics elevated brain CYP2D6 expression may contribute to altered sensitivity to centrally acting drugs and to the mediation of neurotoxic and behavioral effects of alcohol...
  62. ncbi CYP2E1*1D regulatory polymorphism: association with alcohol and nicotine dependence
    Lisa A Howard
    Department of Pharmacology, University of Toronto, Ontario, Canada
    Pharmacogenetics 13:321-8. 2003
    ....
  63. ncbi The effect of methoxsalen on nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism in vivo
    Edward M Sellers
    Department of Pharmacology, and Centre for Research in Women s Health, University of Toronto, Ontario, Canada
    Nicotine Tob Res 5:891-9. 2003
    ..CYP2A6 inhibition may have potential as an exposure reduction or cessation strategy in tobacco dependence...
  64. pmc Brain CYP2E1 is induced by nicotine and ethanol in rat and is higher in smokers and alcoholics
    Lisa A Howard
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8
    Br J Pharmacol 138:1376-86. 2003
    ..1-10 nM). 5. CYP2E1 induction in the brain, by ethanol or nicotine, may influence the central effects of ethanol and the development of nervous tissue pathologies observed in alcoholics and smokers...
  65. ncbi Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR
    Gail McKeown-Eyssen
    Departments of Public Health Sciences, University of Toronto, ON, Canada
    Int J Epidemiol 33:971-8. 2004
    ..Because genetic variation alters the rate of chemical metabolism, this study was designed to determine if MCS cases differed from controls for genetic polymorphisms in drug-metabolizing enzymes...
  66. pmc Dopaminergic signaling mediates the motivational response underlying the opponent process to chronic but not acute nicotine
    Taryn E Grieder
    Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    Neuropsychopharmacology 35:943-54. 2010
    ..We suggest that the alleviation of nicotine withdrawal primarily may be driving nicotine motivation in dependent animals...
  67. ncbi Human CYP2D6 and mouse CYP2Ds: organ distribution in a humanized mouse model
    Sharon L Miksys
    Department of Pharmacology, 1 King s College Circle, Toronto, ON, Canada, M5S 1A8
    Drug Metab Dispos 33:1495-502. 2005
    ..This transgenic mouse model is useful for investigating CYP2D6-mediated metabolism in liver, kidney, and especially the intestine, where expression patterns demonstrated substantial species differences...
  68. ncbi Metabolism of 18-methoxycoronaridine, an ibogaine analog, to 18-hydroxycoronaridine by genetically variable CYP2C19
    Wenjiang Zhang
    Center for Addiction and Mental Health, University of Toronto, Toronto, Canada
    Drug Metab Dispos 30:663-9. 2002
    ..The apparent selectivity of this pathway for CYP2C19 suggests 18-MC as a potentially useful probe of CYP2C19 activity in vitro and in vivo...
  69. ncbi Genetic influences on smoking: a brief review
    Nael Al Koudsi
    Department of Pharmacology, Centre for Addiction and Mental Health, University of Toronto, Canada
    Ther Drug Monit 27:704-9. 2005
    ..Significant advances have been made in understanding the genetic contribution to smoking behaviors. These and future studies will provide potential directions for novel prevention and treatment strategies...
  70. ncbi Regional and cellular distribution of CYP2E1 in monkey brain and its induction by chronic nicotine
    Meenal Joshi
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, ON, Canada M5S 1A8
    Neuropharmacology 50:568-75. 2006
    ..Increased CYP2E1 in brain may contribute to oxidative stress and alter localized metabolism, and resulting pharmacology, of centrally acting drugs metabolized by CYP2E1...
  71. pmc Breaking barriers in the genomics and pharmacogenetics of drug addiction
    M K Ho
    Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    Clin Pharmacol Ther 88:779-91. 2010
    ..As genetic testing becomes more common in the practice of medicine, a variety of ethical and practical challenges, some of which are unique to drug addiction, will also need to be considered...
  72. doi Independent and combined effects of ethanol self-administration and nicotine treatment on hepatic CYP2E1 in African green monkeys
    C S Ferguson
    Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada
    Drug Metab Dispos 39:2233-41. 2011
    ..These results have important implications for public health, given the association between elevated CYP2E1 and disease, and the large proportion of individuals who are exposed to ethanol and nicotine, often in combination...
  73. doi Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent
    Jill C Mwenifumbo
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Hum Mutat 29:679-88. 2008
    ..These findings are important for increasing the accuracy of association studies between CYP2A6 genotype and behavioral, disease, or pharmacological phenotypes...
  74. ncbi Rat brain CYP2B induction by nicotine is persistent and does not involve nicotinic acetylcholine receptors
    Jibran Y Khokhar
    Centre for Addiction and Mental Health CAMH, Toronto, and Departments of Pharmacology and Toxicology and Psychiatry, University of Toronto, Toronto, Ontario, Canada
    Brain Res 1348:1-9. 2010
    ..Humans or animals exposed to nicotine may have altered therapeutic drug response, brain levels of neurotransmitters and/or neurotoxicity...
  75. ncbi Induction of the drug metabolizing enzyme CYP2D in monkey brain by chronic nicotine treatment
    Amandeep Mann
    Centre for Addiction and Mental Health, University of Toronto, Canada M5S 1A8
    Neuropharmacology 55:1147-55. 2008
    ..Smokers, or those using nicotine treatment, may have higher levels of brain CYP2D6 that may result in altered localized CNS drug metabolism and inactivation of neurotoxins...
  76. pmc A novel CYP2A6 allele (CYP2A6*35) resulting in an amino-acid substitution (Asn438Tyr) is associated with lower CYP2A6 activity in vivo
    Nael Al Koudsi
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    Pharmacogenomics J 9:274-82. 2009
    ..In conclusion, we identified three novel CYP2A6 alleles (CYP2A6(*)35, (*)36 and (*)37); the higher allele frequency variant CYP2A6(*)35 was associated with lower CYP2A6 activity...
  77. ncbi Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice
    Eric C K Siu
    Department of Pharmacology, University of Toronto, 1 King s College Circle, Room 4326, Toronto, Ontario, Canada
    J Pharmacol Exp Ther 324:992-9. 2008
    ..Our findings suggest that an additional potential mechanism of selegiline in smoking cessation is through inhibition of nicotine metabolism...
  78. ncbi The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs and genetics
    Sharon Miksys
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Drug Metab Rev 36:313-33. 2004
    ..It holds promise for furthering our undestanding of inter-individual variability in response to centrally acting drugs as well as risk for neurological diseases and pathogies...
  79. ncbi Designer drugs that are potent inhibitors of CYP2D6
    David Pritzker
    Department of Pharmacology, University of Toronto, Canada
    J Clin Psychopharmacol 22:330-2. 2002
    ..No CYP2D6-mediated metabolites were detected for either compound. Concurrent oral use of CYP2D6 substrates with MPPP and PEPAP may represent a kinetic drug interaction risk, but this risk must be confirmed clinically...
  80. pmc Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein
    Anna M Lee
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Medical Sciences Building, Room 4336, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Br J Pharmacol 148:786-94. 2006
    ..This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine...
  81. ncbi Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain
    Sharon Miksys
    Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Neuropharmacology 45:122-32. 2003
    ..Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine...
  82. ncbi Phenobarbital induces monkey brain CYP2E1 protein but not hepatic CYP2E1, in vitro or in vivo chlorzoxazone metabolism
    Anna M Lee
    The Centre for Addiction and Mental Health, and the Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Eur J Pharmacol 552:151-8. 2006
    ..This data indicates that phenobarbital does not alter hepatic metabolism, but may alter metabolism of CYP2E1 substrates within the brain...
  83. pmc Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys
    R T Miller
    Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Departments of Psychiatry, Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
    Br J Pharmacol 171:3077-88. 2014
    ..We investigated the independent and combined effects of chronic ethanol self-administration and nicotine treatment on CYP2D expression in African green monkeys...
  84. ncbi Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates
    Y Ramamoorthy
    Department of Pharmacology, University of Toronto, Toronto, Canada
    Pharmacogenetics 11:477-87. 2001
    ....
  85. ncbi Pharmacogenetics of drug dependence: role of gene variations in susceptibility and treatment
    Jibran Y Khokhar
    The Center for Addiction and Mental Health and the Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada
    Annu Rev Pharmacol Toxicol 50:39-61. 2010
    ..This review highlights examples of genetic variations that are important in the development and maintenance of specific drug dependencies as well as those that affect the response to treatment...
  86. pmc Socioeconomic and drug use determinants of smoking status in an urban adult population of Black African descent
    Jill C Mwenifumbo
    The Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Nicotine Tob Res 10:1319-25. 2008
    ..001). Overall, lower education levels, divorce, and alcohol and marijuana use were significantly associated with increased likelihood of smoking among this population...
  87. ncbi Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients
    Vincenzo De Luca
    Neurogenetics Section, Clarke Site, Centre for Addiction and Mental Health, Department of Psychiatry, Toronto, Ontario, Canada
    Neuropsychopharmacology 29:1522-6. 2004
    ..37, 3 df, p=0.015). Although this novel finding requires replication, it suggests that further study into the relationship between schizophrenia and nicotine system genes is warranted...
  88. ncbi Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro
    Wenjiang Zhang
    Department of Pharmacology, University of Toronto, Ontario, Canada
    Drug Metab Dispos 31:768-72. 2003
    ....
  89. ncbi Reduced (+/-)-3,4-methylenedioxymethamphetamine ("Ecstasy") metabolism with cytochrome P450 2D6 inhibitors and pharmacogenetic variants in vitro
    Yamini Ramamoorthy
    Department of Pharmacology, University of Toronto, Ont, Canada
    Biochem Pharmacol 63:2111-9. 2002
    ..These individuals, and those taking CYP2D6 inhibitors, may demonstrate altered acute and/or long-term MDMA-related toxicity...
  90. doi Effect of metabolic blockade on the psychoactive effects of dextromethorphan
    Laurie A Zawertailo
    Centre for Addiction and Mental Health, Nicotine Dependence Clinic, Toronto, Ontario, Canada
    Hum Psychopharmacol 25:71-9. 2010
    ..This study examined whether pharmacological inhibition of CYP2D6 activity with quinidine would mimic the genetic mutation and thus also alter the psychoactive effects of DM...
  91. ncbi The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: studies of drug use and dependence in Caucasians
    Rachel F Tyndale
    Department of Pharmacology, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada
    Am J Med Genet B Neuropsychiatr Genet 144:660-6. 2007
    ..These results, particularly the observation of altered risk for sedative drug use, should be investigated further in multiple ethnic populations...
  92. ncbi Ethnic variability in the allelic distribution of human aryl hydrocarbon receptor codon 554 and assessment of variant receptor function in vitro
    J M Wong
    Department of Pharmacology, University of Toronto, Ontario, Canada
    Pharmacogenetics 11:85-94. 2001
    ..It is not yet known if any of the wide variations in allele frequency at codon 554 are related to ethnic differences in susceptibility to adverse effects of environmental chemicals...
  93. ncbi Cytochrome P450 2D6 enzyme neuroprotects against 1-methyl-4-phenylpyridinium toxicity in SH-SY5Y neuronal cells
    Amandeep Mann
    The Centre for Mental Health and Addictions, and Centre for Addiction and Mental Health Room 4326, University of Toronto, 1 Kings College Circle, Toronto, ON, Canada, M5S 1A8
    Eur J Neurosci 31:1185-93. 2010
    ..These data further support a possible role for CYP2D6 in neuroprotection from Parkinson's disease-causing neurotoxins, especially in the human brain where expression of CYP2D6 is high in some regions (e.g. substantia nigra)...
  94. ncbi Inhibition of cytochromes P450 by antifungal imidazole derivatives
    Wenjiang Zhang
    Department of Pharmacology, University of Toronto, Ontario, Canada
    Drug Metab Dispos 30:314-8. 2002
    ..4 microM), and CYP3A4 (clotrimazole K(i), 0.02 microM; miconazole K(i), 0.03 microM; tioconazole K(i), 0.02 microM). Therefore, this class of compounds is likely to result in significant drug-drug interactions in vivo...
  95. ncbi The role of pharmacogenetically-variable cytochrome P450 enzymes in drug abuse and dependence
    Lisa A Howard
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8
    Pharmacogenomics 3:185-99. 2002
    ....
  96. ncbi Treatment of codeine dependence with inhibitors of cytochrome P450 2D6
    Leona C Fernandes
    Sunnybrook and Women s College Health Sciences Centre, Women s College Campus, Toronto, Ontario, Canada
    J Clin Psychopharmacol 22:326-9. 2002
    ..In this small sample, CYP2D6 inhibitors did not appear to have a useful role in the treatment of codeine dependence...
  97. pmc Relationship between CYP2A6 and CHRNA5-CHRNA3-CHRNB4 variation and smoking behaviors and lung cancer risk
    Catherine A Wassenaar
    Centre for Addiction and Mental Health, Department of Psychiatry, Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Bldg, Rm 4326, 1 King s College Circle, Toronto, ON M5S 1A8, Canada
    J Natl Cancer Inst 103:1342-6. 2011
    ..CYP2A6 and CHRNA5-A3-B4 appear to be more strongly associated with smoking behaviors and lung cancer risk, respectively...
  98. ncbi An association of CYP2A6 genotype and smoking topography
    Andrew A Strasser
    Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Nicotine Tob Res 9:511-8. 2007
    ..The results from this study also suggest a behavioral mechanism that may account for reduced cancer risk in slow metabolizers...
  99. ncbi Factors influencing cotinine half-life during smoking abstinence in African American and Caucasian women
    Karen L Ahijevych
    Ohio State University College of Nursing, Columbus 43210, USA
    Nicotine Tob Res 4:423-31. 2002
    ..To improve accuracy in correctly classifying non-smokers with cotinine levels, a period of at least 7 days of smoking abstinence may be warranted...
  100. ncbi Nicotine metabolism: the impact of CYP2A6 on estimates of additive genetic influence
    Gary E Swan
    Center for Health Sciences, SRI International, Menlo Park, California 94025, USA
    Pharmacogenet Genomics 15:115-25. 2005
    ..These results suggest the involvement of additional genetic factors (e.g. uncharacterized or novel CYP2A6 alleles as well as other genes in the metabolic pathway) that remain to be identified...
  101. ncbi The role of CYP2A6 in the emergence of nicotine dependence in adolescents
    Janet Audrain-McGovern
    Tobacco Use Research Center, Department of Psychiatry, University of Pennsylvania, 3535 Market St, Philadelphia, PA 19104, USA
    Pediatrics 119:e264-74. 2007
    ....