methimazole and octylamine

methimazole has been researched along with octylamine* in 6 studies

Other Studies

6 other study(ies) available for methimazole and octylamine

ArticleYear
In vitro confirmation of selegiline N-oxidation by flavin-containing monooxygenase in rat microsome using LC-ESI MS.
    Biological & pharmaceutical bulletin, 2004, Volume: 27, Issue:10

    In order to investigate the conversion of selegiline (SG), a drug used in the treatment of Parkinson's disease, to selegiline N-oxide (SGO) as a major metabolic pathway for SG, rat liver microsomal incubations were carried out in vitro in the presence of NADPH. SG was transformed into SGO in vitro as described in our previous human in vivo experiment. In the kinetic studies, the Vmax/Km value of the N-oxidation at pH 8 was found to be approximately four times greater than that at pH 7.4. The N-oxidation was also found to be inhibited by methimazole, an inhibitor of the flavin-containing monooxigenase (FMO) rather than by SKF 525A, an inhibitor of cytochrome P450s, and stimulated approximately two times by n-octylamine, an stimulator of FMO. Moreover, the N-oxidation activity remained almost unchanged in the presence of NADPH even after heating at 50 degrees C for a few minutes. The present data demonstrate that the N-oxidation of SG to SGO is principally mediated by FMO.

    Topics: Amines; Animals; Antiparkinson Agents; Chromatography, Liquid; Enzyme Inhibitors; Heating; Hydrogen-Ion Concentration; In Vitro Techniques; Methimazole; Microsomes, Liver; NADP; Oxidation-Reduction; Oxygenases; Proadifen; Rats; Selegiline; Spectrometry, Mass, Electrospray Ionization

2004
Modulation of human flavin-containing monooxygenase 3 activity by tricyclic antidepressants and other agents: importance of residue 428.
    Archives of biochemistry and biophysics, 1998, Oct-01, Volume: 358, Issue:1

    Human flavin-containing monooxygenase 3 (FMO3) is subject to modulation by tricyclic antidepressants and other agents. Imipramine activates FMO3-catalyzed metabolism of methimazole at all substrate concentrations tested. This distinguishes FMO3 from rabbit FMO1 and FMO2, which are activated at high substrate concentration and inhibited at low substrate concentration, and pig FMO1, which is inhibited at all substrate concentrations. The response of FMO3 is also unique in that chlorpromazine is markedly more effective as a modulator than is imipramine. n-Octylamine, MgCl2, and HgCl2 all inhibit FMO3, the first two in a biphasic manner. Substitution of lysine for threonine at position 428 significantly alters the response of FMO3 to modulators without changing the kinetic parameters for the metabolism of the substrate. Activation by imipramine and chlorpromazine is reduced or abolished and inhibition, most obvious at low substrate concentrations, is observed. This is consistent with elimination of self-activation in the metabolism of imipramine. The mutation at 428 also eliminates the biphasic nature of the inhibition by n-octylamine and MgCl2, but does not alter the effect of HgCl2. Our findings show that the activity of FMO3 can be modulated by large drug molecules as well as short-chain amines and metal ions. This modulation can be markedly altered by changing a single amino acid in the enzyme.

    Topics: Amines; Amino Acid Substitution; Antidepressive Agents, Tricyclic; Catalysis; Chlorpromazine; Enzyme Activation; Humans; Imipramine; Lysine; Magnesium Chloride; Mercuric Chloride; Methimazole; Mutagenesis, Site-Directed; Oxygenases; Threonine

1998
The S-oxidation of thioamides by rat liver microsomes.
    Biochemical Society transactions, 1991, Volume: 19, Issue:2

    Topics: Amines; Animals; Ethionamide; Kinetics; Male; Methimazole; Metyrapone; Microsomes, Liver; Mixed Function Oxygenases; NADP; Niacinamide; Oxidation-Reduction; Proadifen; Rats; Rats, Inbred Strains

1991
Role of formaldehyde hydrazone and catalase in hydrazine-induced methylation of DNA guanine.
    Carcinogenesis, 1988, Volume: 9, Issue:1

    Hydrazine is acutely neurotoxic, hepatotoxic and nephrotoxic; it is also carcinogenic to liver and lung in rodents. Administration of hydrazine results in formation of 7-methylguanine and O6-methylguanine in target organ DNA of rats, mice, hamsters and guinea-pigs. It has been suggested that hydrazine reacts with endogenous formaldehyde to form a condensation product which could be metabolized to a methylating agent. Solutions of 0.50 mM hydrazine and formaldehyde have, upon mixing, NMR spectra (300 MHz) consistent with the formation of formaldehyde hydrazone but not other possible condensation products such as tetraformyltriazine or formaldehyde azine. These same solutions evidencing hydrazone formation, when incubated in an in vitro system containing post-mitochondrial (S9), microsomal, cytosolic or mitochondrial cell fractions, resulted in the methylation of DNA guanine; S9 was the most active fraction. Neither the P-450 monooxygenase nor flavin monooxygenase systems appeared to be important in hydrazine/formaldehyde-induced methylation of DNA. However, sodium azide, cyanamide and carbon monoxide all inhibited S9-supported DNA methylation. Bovine liver catalase, a heme-containing cytochrome, readily transformed hydrazine/formaldehyde to a methylating agent. The data support formation of formaldehyde hydrazone as the condensation product of hydrazine and formaldehyde which is rapidly transformed in various liver cell fractions, perhaps by catalase and/or catalase-like enzymes, to a methylating agent.

    Topics: Amines; Animals; Catalase; DNA; Formaldehyde; Guanine; Heterocyclic Compounds; Hydrazines; Hydrazones; Magnetic Resonance Spectroscopy; Male; Methimazole; Methylation; Rats; Rats, Inbred Strains

1988
Formation of two major nicotine metabolites in livers of guinea pigs.
    Biochemical pharmacology, 1987, Dec-15, Volume: 36, Issue:24

    Using antibody against NADPH-cytochrome P-450 reductase and several effectors of cytochrome P-450 and FAD-containing monooxygenase, we investigated nicotine metabolites formed by these two enzymes. When [3H]nicotine was metabolized by the combination of liver microsomes of guinea pigs and partially purified aldehyde oxidase, three distinct spots corresponding to nicotine, cotinine and nicotine-1'-oxide were observed on fluorograms of thin-layer chromatography. Antibody against NADPH-cytochrome P-450 reductase inhibited the formation of cotinine but not nicotine-1'-oxide. Metyrapone and n-octylamine inhibited the cotinine formation, while methimazole prevented the formation of nicotine-1'-oxide. These results show that microsomal electron transport systems participate in the formation of nicotine-1'-oxide and strongly suggest the involvement of FAD-containing monooxygenase in the formation of nicotine-1'-oxide.

    Topics: Amines; Animals; Cotinine; Cyclic N-Oxides; Electron Transport; Flavin-Adenine Dinucleotide; Guinea Pigs; Immunologic Techniques; Liver; Methimazole; Metyrapone; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Nicotine; Oxidation-Reduction

1987
Routes to the formation of N-methyl-4-aminophenol, a metabolite of N,N-dimethylaniline.
    Advances in experimental medicine and biology, 1981, Volume: 136 Pt B

    Topics: Amines; Aminophenols; Aniline Compounds; Animals; Biotransformation; Carbon Monoxide; Guinea Pigs; Kinetics; Male; Methimazole; Microsomes, Liver; Polychlorinated Biphenyls; Proadifen; Structure-Activity Relationship; Superoxide Dismutase

1981