ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2011
Drug metabolism within the brain changes drug response: selective manipulation of brain CYP2B alters propofol effects.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 54 citations in OpenAlex.
- Functional impact of high-altitude hypoxia on central nervous system drug transport: integrated analysis of blood-brain barrier permeability, drug transporter/enzyme expression, and pharmacokinetics.Fluids and barriers of the CNS · 2026Article
- Comparative analysis of sex-based, vendor-based, and species differences in cytochrome P450 metabolism.Scientific reports · 2026Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Human CYP2D6 varies across the estrous cycle in brains of transgenic mice altering drug response.Progress in neuro-psychopharmacology & biological psychiatry · 2024Article
- Characterization of the Stereoselective Disposition of Bupropion and Its Metabolites in Rat Plasma and Brain.European journal of drug metabolism and pharmacokinetics · 2023Article
- Beyond the label: current evidence and future directions for the interrelationship between electronic cigarettes and mental health.Frontiers in psychiatry · 2023Review
- Drug-Metabolizing Cytochrome P450 Enzymes Have Multifarious Influences on Treatment Outcomes.Clinical pharmacokinetics · 2021Review
- Human CYP2D6 in the Brain Is Protective Against Harmine-Induced Neurotoxicity: Evidence from Humanized CYP2D6 Transgenic Mice.Molecular neurobiology · 2020Article
- The need for mathematical modelling of spatial drug distribution within the brain.Fluids and barriers of the CNS · 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
- Article
- Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects.BioMed research international · 2018Review
- Brain CYP2B induction can decrease nicotine levels in the brain.Addiction biology · 2017Article
- Pathophysiological implications of neurovascular P450 in brain disorders.Drug discovery today · 2016Review
- Article
- Nicotine regulates the expression of UDP-glucuronosyltransferase (UGT) in humanized UGT1 mouse brain.Drug metabolism and pharmacokinetics · 2015Article
- "Target-Site" Drug Metabolism and Transport.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Nicotine Increases Codeine Analgesia Through the Induction of Brain CYP2D and Central Activation of Codeine to Morphine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys.British journal of pharmacology · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Drug-metabolizing cytochrome P450 (CYPs) enzymes are expressed in the liver, as well as in extrahepatic tissues such as the brain. Here we show for the first time that drug metabolism by a CYP within the brain, illustrated using CYP2B and the anesthetic propofol (2, 6-diisopropylphenol, Diprivan), can meaningfully alter the pharmacological response to a CNS acting drug. CYP2B is expressed in the brains of animals and humans, and this CYP isoform is able to metabolize centrally acting substrates such as propofol, ecstasy, and serotonin. Rats were given intracerebroventricularly (i.c.v.) injections of vehicle, C8-xanthate, or 8-methoxypsoralen (CYP2B mechanism-based inhibitors) and then tested for sleep time following propofol (80 mg/kg intraperitoneally). Both inhibitors significantly increased sleep-time (1.8- to 2-fold) and brain propofol levels, while having no effect on plasma propofol levels. Seven days of nicotine treatment can induce the expression of brain, but not hepatic, CYP2B, and this induction reduced propofol sleep times by 2.5-fold. This reduction was reversed in a dose-dependent manner by i.c.v. injections of inhibitor. Sleep times correlated with brain (r=0.76, P=0.0009), but not plasma (r=0.24, P=0.39) propofol concentrations. Inhibitor treatments increased brain, but not plasma, propofol levels, and had no effect on hepatic enzyme activity. These data indicate that brain CYP2B can metabolize neuroactive substrates (eg, propofol) and can alter their pharmacological response. This has wider implications for localized CYP-mediated metabolism of drugs, neurotransmitters, and neurotoxins within the brain by this highly variable enzyme family and other CYP subfamilies expressed in the brain.
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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.