DIFFERENCE IN EPOXIDES FORMATION AND THEIR FURTHER METABOLISM BETWEEN Δ^9 -AND Δ^8-TETRAHYDROCANNABINOLS BY HUMAN LIVER MICROSOMES

スポンサーリンク

概要

• 論文の詳細を見る

• In vitro metabolism of Δ^9-and Δ^8-tettahydrocannabinols (THCs) was studied using human liver microsomes. Δ^9-orΔ^8-THC was incubated with microsomes in the presence of NADPH-generating system. The metabolites formed were extracted with ethyl acetate, separated by preparative thin-layer chromatography, and identified as trimethylsilyl derivatives by gas chromatography-mass spectrometry. 9α, 10α-Epoxyhexahydrocannabinol (EHHC) together with four monohydroxylated metabolites was formed from Δ^9-THC. The epoxide was found to resist the hydrolysis by epoxide hydrolase, and was further converted to several metabolites by monooxygenase system involving cytochrome P-450. On the other hand, 8β, 9α-dihydroxyhexahydrocannabinol (diOH-HHC) instead of epoxy metabolites was formed from Δ^8-THC under the conditions for monooxygenase. When 1,1,1-trichloropropene-2,3-oxide was further added to the incubation mixture, both of 8α, 9α- and 8β, 9β-EHHCs were found to be formed from Δ^8-THC. These epoxides of Δ^8-THC were preferentially hydrolyzed to 8β, 9α-diOH-HHC by epoxide hydrolase. These results indicate that 9α, 10α-EHHC formed from Δ^9-THC is further metabolized not by epoxide hydrolase but by monooxygenase system involving cytochrome P-450,and that, on the contrary, 8α, 9α-and 8β, 9β-EHHCs derived from Δ^8-THC may be metabolized by epoxide hydrolase rather than cytochrome P-450 in the human liver, forming 8β, 9α-diOH-HHC.

• 社団法人日本薬学会の論文

著者

• 中村 紳一郎

  Specialty Chemicals Research Center Shin-etsu Chemical Co. Ltd.

• YAMAMOTO IKUO

  Department of Laboratory Medicine, Miyazaki Medical College

• Watanabe Kazuhito

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• YOSHIMURA Hidetoshi

  Department of Food and Nutrition, Nakamura Gakuen University

• Yamamoto Ikuo

  北陸大学 薬 衛化

• Yamamoto Ikuo

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Nakamura S

  Specialty Chemicals Research Center Shin-etsu Chemical Co. Ltd.

• NARIMATSU SHIZUO

  Departments of Hygienic Chemistry

• SHIMONISHI TATSUYUKI

  Department of Hygienic Chemistry, School of Pharmacy, Hokuriku University

• Nakamura Satoko

  Osaka University Of Pharmaceutical Sciences

• Watanabe Kazuhito

  Department Of Chemistry And Chemical Engineering Faculty Of Engineering Yamagata University

• Yoshimura Hidetoshi

  Department Of Food And Nutrition Nakamura Gakuen University

• Narimatsu Shizuo

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Watanabe Kazuhito

  Faculty Of Pharmaceutical Sciences Kyushu University

• Yoshimura Hidetoshi

  Department Of Food And Nutrition Nakamura Gakuen

• Yamamoto Ikuo

  Department Of Bioapplied Chemistry Faculty Of Engineering Osaka City University

• Shimonishi Tatsuyuki

  School Of Pharmacy Hokuriku University

関連論文

• Effect of Psychotropic Drugs on the 21-Hydroxylation of Neurosteroids, Progesterone and Allopregnanolone, Catalyzed by Rat CYP2D4 and Human CYP2D6 in the Brain(Biochemistry)
• Differential Expression of Dipeptidyl Peptidase IV (CD26)and Thyroid Peroxidase in Neoplastic Thyroid Tissues
• Butyrylcholinesterase and Erythrocyte Sulfhydryl-dependent Enzyme Hydrolyze Gabexate in Human Blood
• Involvement of Human Blood Arylesterases and Liver Microsomal Carboxylesterases in Nafamostat Hydrolysis
• P2-18 Golgi retention mechanism of CALNUC : NH2-terminal proline plays an essential role for retention
• Effect of Several Cellulosic Binders on Particle Size Distribution in Fluidized Bed Granulation
• Effect of Several Cellulosic Binders on Particle Size Distribution of Granules Prepared by a High-Speed Mixer
• Hepatic Metabolism of Methyl Anthranilate and Methyl N-Methylanthranilate as Food Flavoring Agents in Relation to Allergenicity in the Guinea Pig
• Stereospecific and Regioselective Hydrolysis of Cannabinoid Esters by ES46.5K, an Esterase from Mouse Hepatic Microsomes, and Its Differences from Carboxylesterases of Rabbit and Porcine Liver(Biochemistry)
• In Vitro Inhibitory Effects of Cannabinoids on Progesterone 17α-Hydroxylase Activity in Rat Testis Microsomes
• Synthesis of N^3-Substituted Uridine and Related Pyrimidine Nucleosides and Their Antinociceptive Effects in Mice
• Major Cytochrome P450 Enzymes Responsible for Microsomal Aldehyde Oxygenation of 11-Oxo-〓^8-tetrahydrocannabinol and 9-Anthraldehyde in Human Liver
• Skin Reaction Induced by Aldehydes for Food Flavoring Agents
• Possible Existence of a Novel Receptor for Uridine Analogues in the Central Nervous System Using Two Isomers, N^3-(S)-(+)-and N^3-(R)-(-)-α-Hydroxy-β-phenethyluridines
• Hypnotic Action of N^3-Substituted Arabinofuranosyluracils on Mice
• Cross-Reactivity of Various Tetrahydrocannabinol Metabolites with a Monoclonal Antibody against Tetrahydrocannabinolic Acid
• A Carbonyl Reductase-Catalyzing Reduction of N^3-Phenacyluridine in Rabbit Liver
• Synthesis and Pharmacological Evaluation in Mice of Halogenated Cannabidiol Derivatives.
• Characterization of Microsomal Alcohol Oxygenase Catalyzing the Oxidation of 7-Hydroxy-Δ^8-tetrahydrocannabinol to 7-Oxo-Δ^8-tetrahydrocannabinol in Rat Liver
• Synthesis and Central Nervous System Depressant Effects of N^3-Substituted 2', 3'-O-Isopropylideneuridines
• Synthesis and Pharmacological Evaluation in Mice of Halogenated Cannabidiol Derivatives
• Pharmacologica Efects in Mice of Anandamide and Its Related Fatty Acid Ethanolamides, and Enhancement of Cataleptogenic Effect of Anandamide by Phenylmethylsulfonyl Fluoride
• Effects of Heavy Oil from the Nakhodka on Hepatic and Pulmonary Enzymes of Mice(PROCEEDINGS OF 24TH SYMPOSIUM ON TOXICOLOGY AND ENVIRONMENTAL HEALTH)
• Synthesis and Pharmacological Activities in Mice of Halogenated Δ^9-Tetrahydrocannabinol Derivatives
• Synthesis and Sedative-Hypnotic Effects of N^3-Allyl-and N^1-Allyl-5,6-substituted 2-Thiouracil Derivatives in Mice
• Effective NADH-Dependent Oxidation of 7β-Hydroxy-Δ^8-tetrahydrocannabinol to the Corresponding Ketone by Japanese Monkey Hepatic Microsomes(Toxicology)
• Monkey Hepatic Microsomal Alcohol Oxygenase: Purification and Characterization of a Cytochrome P450 Enzyme Catalyzing the Stereoselective Oxidation of 7α-and 7β-Hydroxy-Δ^8-tetrahydrocannabinol to 7-Oxo-Δ^8-tetrahydrocannabinol
• A Cytochrome P450 Enzyme Responsible for the Carbon Monoxide Formation by Cannabidiol in Mouse Hepatic Microsomes.
• Inhibition of Mouse Hepatic Glutathione S-Transferase by Δ^8-Tetrahydrocannabinol p-Quinone and Cannabidiol Hydroxy-quinone.
• Microsomal Aldehyde Oxygenase (MALDO) for Tolualdehydes, Active Metabolites of Xylenes, in the Mouse Liver and Lung
• "B-4 Hydrolysis of Xenobiotics by ES46.5K, a Novel Esterase from Mouse Liver Microsomes
• Stereoselectivity in Bunitrolol 4-Hydroxylation in Liver Microsomes from Marmosets and Japanese Monkeys
• Microsomal Aldehyde Oxygenase (MALDO): Purification and Characterization of a Cytochrome P450 Isozyme Responsible for Oxidation of 9-Anthraldehyed to 9-Anthracenecarboxylic Acid in Monkey Liver
• A-3 PHARMACOTOXICITY OF A NITROGEN CONTAINING CONSTITUENT IN CANNABIS SATIVA L. : II FERUROYLTYRAMINE AS A NEW CONSTITUENT
• Determination of Heavy Metal Contents in Human Gallstones Using X-Ray Fluorescence Spectrometry (Regular Presentations) (Proceedings of the 15 th Symposium on Environmental Pollutants and Toxicology)
• B05 Pharmacotoxicity of p-Coumaroyltyramine, A Nitrogen Containing Constituent in Cannabis sativa L.
• Determination of Metal Contents in River Sediment Near a Closed Mine by X-ray Fluorescence Spectrometry (Proceedings of the 14th Symposium on Environmental Pollutants and Toxicology)
• Determination of Metal Contents in Biological and Environmental Materials by Energy-Dispersive X-Ray Fluorescence Analysis
• CADMIUM, COPPER AND ZINC CONCENTRATIONS IN HUMAN RENAL CALCULUS AND GALL STONE, AND ITS ANALYTICAL IMPLICATIONS
• MECHANISM OF SLEEP-PROLONGATING EFFECT OF Δ^8-TETRAHYDROCANNABINOL (Δ^8-THC) AND ITS METABOLITES
• IDENTIFICATION AND DETERMINATION OF 11-OXO-Δ^8-TETRAHYDROCANNABINOL AS AN INTERMEDIATE METABOLITE OF Δ^8-TETRAHYDROCANNABINOL IN THE MOUSE BRAIN AND LIVER
• UDP-GLUCURONYLTRANSFERASE ACTIVITIES OF RABBIT LIVER MICROSOMES FOR CANNABINOIDS
• METABOLIC CONVERSION OF Δ^8-TETRAHYDROCANNABINOL (Δ^8-THC) TO Δ^8-THC-11-OIC ACID AND ITS PHARMACOLOGICAL IMPLICATIONS
• METABOLISM OF 11-HYDROXY-Δ^8-THC TO 11-OXO-Δ^8THC IN RATS (The Fourth Meeting for the Study of Toxic Effect)
• Critical Anomaly of the Third-Order Elastic Constants in CsPbCl_3
• Mechanism of Inhibitory Effects of Cannabidiol and Cannabidiol Hydroxy-quinone on the Hepatic Microsomal Drug-Metabolizing Enzymes in Mice (Proceedings of the 23rd Symposium on Toxicology and Environmental Health)
• Involvement of a Novel Mouse Hepatic Microsomal Esterase, ES46.5K, in the Hydrolysis of Phthalate Esters
• Mechanism of Hepatic Microsomal Oxidation of 11-Hydroxy-Δ^8-tetra-hydrocannabinol to 11-Oxo-Δ^8-tetrahydrocannabinol. Evidence for Hydration of the Aldehyde Formed
• Inhibitory Effect of Cannabidiol Hydroxy-quinone, and Oxidative Product of Cannabidiol, on the Hepatic Microsomal Drug-Metabolizing Enzymes of Mice
• INTERACTION OF CANNABINOIDS WITH HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM IN THE RAT
• PURIFICATION AND CHARACTERIZATION OF MOUSE HEPATIC MICROSOMAL ALDEHYDE OXYGENASE
• MECHANISM OF CANNABIELSOIN FORMATION FROM CANNABIDIOL, ONE OF THE MAJOR CMPONENTS OF MARIHUANA
• CYTOCHROME P450 ISOZYMES INVOLVED IN METABOLIC ACTIVATION OF Δ^9-TETRAHYDROCANNABINOL BY RAT LIVER MICROSOMES
• Mechanism of Biological Formation of Cannabielsoin from Cannabidiol in the Guinea-Pig, Mouse, Rat and Rabbit
• HEPATIC MICROSOMAL OXYGENATION OF METHYL GROUP TO CARBOXYLIC ACID IN XENOBIOTICS : METABOLISM OF Δ^8-TETRAHYDROCANNABINOL AT THE 11-POSITION
• Identification of Cannabielsoin, a New Metabolite of Cannabidiol Formed by Guinea-Pig Hepatic Microsomal Enzymes, and Its Pharmacological Activity in Mice
• IN VIVO EFFECTS OF TETRAHYDROCANNABINOLS AND THEIR EIGHT MONOOXYGENATED METABOLITES ON THE HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEMS OF MICE
• METABOLIC ACTIVATION OF CANNABIDIOL BY HEPATIC MICROSOMES. COMPLEX FORMATION WITH CYTOCHROME P-450
• MECHANISM OF THE PROLONGATION OF BARBITURATE-INDUCED SLEEPING TIME AND THE INHIBITION OF THE HEPATIC MICROSOMAL DRUG METABOLIZING ENZYMES BY CANNABIDIOL, A COMPONENT OF CANNABIS
• EFFECTS OF TWO CANNABINOIDS ON HEPATIC MICROSOMAL CYTOCHROME P-450
• METABOLIC ACTIVATION OF Δ^8-THTRAHYDROCANNABINOL (Δ^8-THC) AT THE 7-POSITION AND MECHANISM OF THE OXIDATION OF 7-HYDROXY-Δ^8-THC TO 7-OXO-Δ^8-THC WITH LIVER MICROSOMES
• METABOLIC DISPOSITION OF 8α, 9α-AND 8β, 9β-EPOXYHEXAHYDROCANNABINOLS IN THE MOUSE
• IN VITRO METABOLISM OF TETRAHYDROCANNABINOL (THC) BY HUMAN LIVER MICROSOMES. EPOXIDE-DIOL PATHWAY OF THC
• DIFFERENCE IN EPOXIDES FORMATION AND THEIR FURTHER METABOLISM BETWEEN Δ^9 -AND Δ^8-TETRAHYDROCANNABINOLS BY HUMAN LIVER MICROSOMES
• THE PROPERTIES OF UDP-GLUCURONYLTRANSFERASE FOR CANNABINOIDS IN RAT LIVER MICROSOMES
• The Synthesis of Isoquinoline Alkaloid and Its Related Compounds Using Alanine Derivatives as Chiral Auxiliaries
• c-Kit Proto-oncogene Is More Likely to Lose Expression in Differentiated Thyroid Carcinoma Than Three Thyroid-specific Genes : Thyroid Peroxidase, Thyroglobulin, and Thyroid Stimulating Hormone Receptor
• Compertitive Inhibition of Δ^8-Tetrahydrocannabinol and Its Active Metabolites for Cannabinoid Receptor Binding
• Anandamide, an Endogenous Cannabinoid Receptor Ligand, Also Interacts with 5-Hydroxytryptamine (5-HT) Receptor
• Synthesis and Hypnotic Activities of 4-Thio Analogues of N^3-Substituted Uridines
• Establishment by Adriamycin Exposure of Multidrug-resistant Rat Ascites Hepatoma AH130 Cells Showing Low DT-diaphorase Activity and High Cross Resistance to Mitomycins
• Inhibition of P-Glycoprotein-Dependent Multidrug Resistance by an Isoquinolinesulfonamide Compound H-87 in Rat Ascites Hepatoma AH66 Cells
• A Novel Series of Thromboxane A_2 Synthetase Inhibitors with Free Radical Scavenging and Anti-peroxidative Activities
• Bioavailable Acyl-CoA : Cholesterol Acyltransferase Inhibitor with Anti-peroxidative Activity : Synthesis and Biological Activity of Novel Indolinyl Amide and Urea Derivatives
• Studies on the Constituents of Broussonetia Species. V. Two New Pyrrolidine Alkaloids, Broussonetines K and L, as Inhibitors of Glycosidase, from Broussonetia Kazinoki SIEB.
• Facile Formation of Chiral Calixarene Analogs Incorporating Cystine Peptide into the Macrocyclic Ring.
• Reductive Dimerization of Alkylidenemalonates Using Samarium(II) Diiodide and ^1H-NMR Behavior of the Dimers, 2,3-Diaryl-1,1,4,4-butanetetracarboxylates
• STRUCTURE-ACTIVITY RELATIONSHIP OF URIDINE DERIVATIVES FOR HYPNOTIC ACTIVITY
• Accurate Measurements and Determination of the Magnetic Anisotropies of Several Manganese Crystals
• INHIBITORY EFFECT OF CANNABIDIOL ON THE HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM IN THE RAT
• Biquadratic Exchange Effect on the Magnetic Anisotropy in a Heisenberg Linear Chain Antiferromagnet [(CH_3)_3NH]MnBr_32H_2O
• EPR g-Shift and Anisotropic Magnetic Susceptibility in K_2MnF_4
• Studies on the Constituents of Broussonetia Species. IV. Two New Pyrrolidinyl Piperidine Alkaloids, Broussonetines I and J, from Broussonetia kazinoki SIEB.
• Studies on the Constituents of Broussonetia Species. III. Two New Pyrrolidine Alkaloids, Broussonetines G and H, as Inhibitors of Glycosidase, from Broussonetia kazinoki SIEB.
• Studies on the Constituents of Broussonetia Species. II. Six New Pyrrolidine Alkaloids, Broussonetine A, B, E, F and Broussonetinine A and B, as Inhibitors of Glycosidases from Broussonetia kazinoki SIEB.
• A pivotal role of IL-12 in T_h 1-dependent mouse liver injury
• Interleukin-12 Augments the Generation of Autologous Tumor-reactive CD8^+ Cytotoxic T Lymphocytes from Tumor-infiltrating Lymphocytes
• Determination of Virial Coefficient of N-isopropylacrylamide Polymer Solution by Light Scattering Measurements
• Brillouin Scattering Study of the Ferroelectric Phase Transition in NH_4LiSO_4
• Fluorometric Determination of Hydrogen Peroxide Based on Formation of Amprochrome
• Rapid Determination of Trace Metals in Foods by Using the Microwave Oven-Digestion Method. II. Determination of Zinc, Copper, Manganese, Lead and Cadmium
• Rapid Determination of Trace Metals in Foods by Using the Microwave Oven-Digestion Method. I. Determination of Arsenic
• DEAMINATION OF AMPHETAMINES BY CYTOCHROMES P450: STUDIES ON SUBSTRATE SPECIFICITY AND REGIOSELECTIVITY WITH MICROSOMES AND PURIFIED CYP2C SUBFAMILY ISOZYMES
• Anomalous Temperature Dependence of the Intensity of Brillouin Scattering near the Ferroelectric Phase Transition Point of NH_4LiSO_4
• TOLERANCE DEVELOPMENT TO HYPOTHERMIC EFFECT OF Δ^8-TETRAHYDROCANNABINOL AND ITS ACTIVE METABOLITES
• METABOLIC DISPOSITION OF 8α, 9α- AND 8β, 9β-EPOXYHEXAHYDROCANNABINOL (EHHC) IN THE MOUSE
• 9α, 10α-EPOXYHEXAHYDROCANNABINOL FORMATION FROM Δ^9-TETRAHYDROCANNABINOL BY LIVER MICROSOMES OF PHENOBARBITAL-TREATED MICE AND ITS PHARMACOLOGICAL ACTIVITIES IN MICE
• IN VITRO METABOLIC FORMATION OF 8α, 9α-EPOXYHEXAHYDROCANNABINOL AND ITS IMPLICATION IN THE PHARMACOLOGICAL ACTIVITY OF Δ^8-TETRAHYDROCANNABINOL
• Structural Requirements for Potent Direct Inhibition of Human Cytochrome P450 1A1 by Cannabidiol: Role of Pentylresorcinol Moiety
• Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells

もっと見る 閉じる

スポンサーリンク