Skip to main content


We're creating a new version of this page. See preview

  • Poster presentation
  • Open Access

Distribution of Cytochrome P450 2D6 in the human brain: potential role in psychotropic drug response

  • 1,
  • 2,
  • 3,
  • 4 and
  • 5
Annals of General Psychiatry20087 (Suppl 1) :S127

  • Published:


  • Constitutive Expression
  • Drug Response
  • Altered Sensitivity
  • Brain Expression
  • CYP2 Induction


The cytochromes P450 (CYP450) 1-3 are involved in 70-80% of all phase-I dependent metabolism of drugs. Highly polymorphic CYP450 2D6 gene is coding biotransformation of about 25% of clinically used medications, including opioid analgesics, antipsychotics and antidepressants. Its liver tissue expression is well investigated, but still controversial information is available regarding the presence in the human brain, as well as the contribution to psychotropic drug actions and adverse drug reactions. This review followed-up the published data according to the localization, regional distribution and protein expression of CYP 2D6 in CNS and analyzed the current information about its role in local drug pharmacokinetics and drug response.

Materials and methods

MEDLINEplus, PubMed, Entrez and Medscape databases and electronic journals were searched for studies on CYP 2D6 in the human brain. Published research articles and reviews on pharmacogenetics of oxidative metabolism and psychotropic drug response were observed for the potential role of CYP 2D6 brain expression.


Reviewed studies demonstrated CYP2D6 distribution, CYP2D6 mRNA and protein constitutive expression in neuronal and glial cells in certain CNS regions [13]. Some data supported differences in brain CYP2 induction, depending on the region, cell type and inducer. CYP2D6 was found to be involved in the brain endogenous substances metabolism and its enzyme activity could be under various regulatory mechanisms with potential influence on drug response [4].


Constitutive expression of CYP2D6 in CNS may create a local environment of drug metabolism, which, along with the potential neurotransmitter modulation, may contribute to altered sensitivity and inter-individual variability in psychotropic drug response.

Authors’ Affiliations

Dept of Physiology, Experimental&Clinical Pharmacology, Faculty of Medicine, Medical University, Pleven, Bulgaria
Psychiatrist, Diagnostic Consultative Centre II, Pleven, Bulgaria
Psychiatrist, Military Medical Academy, Department of Psychiatry, Sofia, Bulgaria
Psychiatrist, Diagnostic Consultative Centre XXVIII, Sofia, Bulgaria
Dept of Physiology, Experimental&Clinical Pharmacology, Faculty of Medicine, Medical University, Pleven, Bulgaria


  1. Hedlund E., Gustafsson J-A., Warner M.: Cytochrome P450 in the Brain. Current Drug Metabolism. 2001, 2: 245-263. 10.2174/1389200013338513.View ArticlePubMedGoogle Scholar
  2. Chinta S., Pai H., Upadhya S., Boyd M., Ravindranath V.: Constitutive expression and localization of the major drug metabolizing enzyme, cytochrome P4502D in human brain. Brain Res Mol Brain Res. 2002, 103 (1-2): 49-61. 10.1016/S0169-328X(02)00177-8.View ArticlePubMedGoogle Scholar
  3. Siegle I., Fritz P., Eckhardt K., Zanger U., Eichelbaum M.: Cellular localization and regional distribution of CYP2D6 mRNA and protein expression in human brain. Pharmacogenetics. 2001, 11 (3): 237-245. 10.1097/00008571-200104000-00007.View ArticlePubMedGoogle Scholar
  4. Miksys S, Tyndale R: The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs and genetics. Drug Metab Rev. 2004, 36 (2): 313-333. 10.1081/DMR-120034149.View ArticlePubMedGoogle Scholar


© Pendicheva et al.; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.