ArticleBiochemical pharmacology2009
Effects of CYP2D6 status on harmaline metabolism, pharmacokinetics and pharmacodynamics, and a pharmacogenetics-based pharmacokinetic model.
Article in Biochemical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies.Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) · 2016Pooled it
- The pharmacological interaction of compounds in ayahuasca: a systematic review.Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)Pooled it
- Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted Therapy.Clinical pharmacology and therapeutics · 2025Review
- Integrated metabolomics and gut microbiota analysis to explore the potential mechanism of levo-tetrahydropalmatine against ketamine addiction.Frontiers in pharmacology · 2025Article
- Ayahuasca: pharmacology, safety, and therapeutic effects.CNS spectrums · 2024Review
- Synergistic antidepressant- and anxiolytic-like effects of harmaline along with cinanserin in acute restraint stress-treated mice.Psychopharmacology · 2021Article
- Human CYP2D6 in the Brain Is Protective Against Harmine-Induced Neurotoxicity: Evidence from Humanized CYP2D6 Transgenic Mice.Molecular neurobiology · 2020Article
- P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Potent inhibition of human organic cation transporter 2 (hOCT2) by β-carboline alkaloids.Xenobiotica; the fate of foreign compounds in biological systems · 2017Article
- Exposure Characteristics of the Analogous β-Carboline Alkaloids Harmaline and Harmine Based on the Efflux Transporter of Multidrug Resistance Protein 2.Frontiers in pharmacology · 2017Article
- Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice.Acta pharmaceutica Sinica. B · 2016Article
- Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years.Therapeutic advances in psychopharmacology · 2016Review
- Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms.Pharmacological reports : PR · 2016Article
- Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors.Neuropharmacology · 2015Article
- Potential role of CYP2D6 in the central nervous system.Xenobiotica; the fate of foreign compounds in biological systems · 2013Article
- Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Harmaline and harmalol inhibit the carcinogen-activating enzyme CYP1A1 via transcriptional and posttranslational mechanisms.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2012Article
- Humanized transgenic mouse models for drug metabolism and pharmacokinetic research.Current drug metabolism · 2011Article
- Drug-metabolizing enzyme, transporter, and nuclear receptor genetically modified mouse models.Drug metabolism reviews · 2011Review
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.Current drug metabolism · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Harmaline is a beta-carboline alkaloid showing neuroprotective and neurotoxic properties. Our recent studies have revealed an important role for cytochrome P450 2D6 (CYP2D6) in harmaline O-demethylation. This study, therefore, aimed to delineate the effects of CYP2D6 phenotype/genotype on harmaline metabolism, pharmacokinetics (PK) and pharmacodynamics (PD), and to develop a pharmacogenetics mechanism-based compartmental PK model. In vitro kinetic studies on metabolite formation in human CYP2D6 extensive metabolizer (EM) and poor metabolizer (PM) hepatocytes indicated that harmaline O-demethylase activity (V(max)/K(m)) was about 9-fold higher in EM hepatocytes. Substrate depletion showed mono-exponential decay trait, and estimated in vitro harmaline clearance (CL(int), microL/min/10(6)cells) was significantly lower in PM hepatocytes (28.5) than EM hepatocytes (71.1). In vivo studies in CYP2D6-humanized and wild-type mouse models showed that wild-type mice were subjected to higher and longer exposure to harmaline (5 and 15mg/kg; i.v. and i.p.), and more severe hypothermic responses. The PK/PD data were nicely described by our pharmacogenetics-based PK model involving the clearance of drug by CYP2D6 (CL(CYP2D6)) and other mechanisms (CL(other)), and an indirect response PD model, respectively. Wild-type mice were also more sensitive to harmaline in marble-burying tests, as manifested by significantly lower ED(50) and steeper Hill slope. These findings suggest that distinct CYP2D6 status may cause considerable variations in harmaline metabolism, PK and PD. In addition, the pharmacogenetics-based PK model may be extended to define PK difference caused by other polymorphic drug-metabolizing enzyme in different populations.
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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.