ArticlePloS one2008
Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 74 citations in OpenAlex.
- Genetic variation in CYP3A43 explains racial difference in olanzapine clearance.Molecular psychiatry · 2011Trial
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism.Pharmacological reviews · 2024Review
- Article
- Changes in Alprazolam Metabolism by CYP3A43 Mutants.Biomedicines · 2022Article
- The Role of CYP3A in Health and Disease.Biomedicines · 2022Review
- Mitochondrial Dysfunction in Rabies Virus-Infected Human and Canine Brains.Neurochemical research · 2022Article
- Human Orphan Cytochromes P450: An Update.Current drug metabolism · 2022Article
- Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry.Molecules (Basel, Switzerland) · 2021Article
- Cannabidiol and Neurodevelopmental Disorders in Children.Frontiers in psychiatry · 2021Review
- Seeking Nonspecific Binding: Assessing the Reliability of Tissue Dilutions for Calculating Fraction Unbound.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- The Interplay between the Endocannabinoid System, Epilepsy and Cannabinoids.International journal of molecular sciences · 2019Review
- Role of vitamin D receptor in the regulation ofActa pharmaceutica Sinica. B · 2019Review
- Comparison of In Vitro Stereoselective Metabolism of Bupropion in Human, Monkey, Rat, and Mouse Liver Microsomes.European journal of drug metabolism and pharmacokinetics · 2019Article
- Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association With Cytochrome P450 3A Polymorphisms.American journal of epidemiology · 2018Article
- CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Genetic variation in CYP3A43 is associated with response to antipsychotic medication.Journal of neural transmission (Vienna, Austria : 1996) · 2015Review
- The potential effect of gender in CYP1A1 and GSTM1 genotype-specific associations with pediatric brain tumor.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- D₂-receptor occupancy measurement of JNJ-37822681, a novel fast off-rate D₂-receptor antagonist, in healthy subjects using positron emission tomography: single dose versus steady state and dose selection.Psychopharmacology · 2012Article
- Oxygen regulates tissue nitrite metabolism.Antioxidants & redox signaling · 2012Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.