Studies on 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine, a nonneurotoxic analogue of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.


:Previous reports indicate that 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine (BMTP), the benzyl analogue of the Parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is not neurotoxic in the C-57 black mouse even when administered at a dose 10 times greater than the dose of MPTP required to cause an 85% depletion of neostriatal dopamine. Intrastriatal microdialysis in the rat with the corresponding 4-benzyl-1-methylpyridinium ion BMP+ for 60 min, however, causes nerve terminal destruction similar to that observed following a 15-min perfusion with the 1-methyl-4-phenylpyridinium ion MPP+, the monoamine oxidase B (MAO-B) generated metabolite derived from MPTP. With the aid of purified beef liver MAO-B and synthetic standards, we observed the efficient and quantitative conversion of BMTP to the corresponding 2,3-dihydropyridinium intermediate BMDP+, which underwent further, but incomplete, oxidation to BMP+. These MPTP-type properties point to in vivo effects, such as pharmacokinetic parameters and/or alternative metabolic pathways, to account for BMTP's lack of neurotoxicity.


Chem Res Toxicol


Naiman N,Rollema H,Johnson E,Castagnoli N Jr




Has Abstract


1990-03-01 00:00:00












  • Quartz Disrupts Iron Homeostasis in Alveolar Macrophages To Impact a Pro-Inflammatory Effect.

    abstract::The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is the cell type resident in the respiratory tract that is most likely to make initial contact with inhaled pa...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Ghio AJ,Soukup JM,Stonehuerner J,Tong H,Richards J,Gilmour MI,Madden MC,Shen Z,Kantrow SP

    更新日期:2019-09-16 00:00:00

  • Locating nucleobase lesions within DNA sequences by MALDI-TOF mass spectral analysis of exonuclease ladders.

    abstract::The location of carcinogen-modified nucleobases (DNA adducts) within DNA sequences is a critical factor affecting their promutagenic properties and persistence in DNA. We now report the use of controlled exonuclease digestion followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MAL...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Tretyakova N,Matter B,Ogdie A,Wishnok JS,Tannenbaum SR

    更新日期:2001-08-01 00:00:00

  • Toxicant Deposition and Transport in Alveolus: A Classical Density Functional Prediction.

    abstract::The deposition and transport of toxicants on pulmonary surfactant are important processes in human health and medical care. We have introduced classical density functional theory (CDFT) to provide insight into this process. Nine typical toxicants in PM2.5 were considered, and their free energy and structural informati...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Liu H,Liu Y,Shang Y,Liu H

    更新日期:2018-12-17 00:00:00

  • Increased levels of inosine in a mouse model of inflammation.

    abstract::One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen, and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage, with these chemical mediators causing damage that ultimately leads to cell death and mutation. To ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Prestwich EG,Mangerich A,Pang B,McFaline JL,Lonkar P,Sullivan MR,Trudel LJ,Taghizedeh K,Dedon PC

    更新日期:2013-04-15 00:00:00

  • In vivo cadmium mobilization by three novel bis(carbodithioates).

    abstract::Four novel cadmium-chelating agents N,N'di(D-glucosyl)alkanediamine-N,N'-bis(carbodithioates) 4a-e were prepared as disodium salts of the general formula (CH2)n[N(CS2Na)CH2(CHOH)4CH2OH]2, where n = 7, 8, 10, and 12. They were synthesized by the reductive coupling of 2 mol of alpha-D-(+)-glucose (1) with 1 mol of the c...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Singh PK,Jones MM,Kostial K,Blanusa M,Piasek M

    更新日期:1996-01-01 00:00:00

  • Chemical analysis and hemolytic activity of the fava bean aglycon divicine.

    abstract::Divicine is an unstable aglycon metabolite of the fava bean pyrimidine beta-glucoside vicine. Divicine has long been thought to be a mediator of an acute hemolytic crisis, known as favism, in susceptible individuals who ingest fava beans (Vicia faba). However, a recent report has questioned the chemical identity of th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: McMillan DC,Schey KL,Meier GP,Jollow DJ

    更新日期:1993-07-01 00:00:00

  • Metabolic activation and major protein target of a 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonist.

    abstract::1-{4-[(4-Phenyl-5-trifluoromethyl-2-thienyl)methoxy]benzyl}azetidine-3-carboxylic acid (MRL-A) is a potent sphingosine-1-phosphate-1 receptor agonist, with potential application as an immunosuppressant in organ transplantation or for the treatment of autoimmune diseases. When administered orally to rats, radiolabeled ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Aloysius H,Tong VW,Yabut J,Bradley SA,Shang J,Zou Y,Tschirret-Guth RA

    更新日期:2012-07-16 00:00:00

  • Detection of sodium channel activators by a rapid fluorimetric microplate assay.

    abstract::Marine toxins such as brevetoxins and ciguatoxins are produced by dinoflagellates and can accumulate in seafood. These toxins affect humans through seafood consumption. Intoxication is mainly characterized by gastrointestinal and neurological disorders and, in most severe cases, by cardiovascular problems. To prevent ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Louzao MC,Vieytes MR,Yasumoto T,Botana LM

    更新日期:2004-04-01 00:00:00

  • Profiling the reactive metabolites of xenobiotics using metabolomic technologies.

    abstract::A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Li F,Lu J,Ma X

    更新日期:2011-05-16 00:00:00

  • Effects of hepatotoxic doses of acetaminophen and furosemide on tissue concentrations of CoASH and CoASSG in vivo.

    abstract::The effects of hepatotoxic doses of acetaminophen on tissue concentrations of CoA in the thiol form (CoASH) and as the corresponding mixed disulfide with GSH (CoASSG) were determined to test the hypotheses that early oxidant effects of acetaminophen are expressed principally in the mitochondrial compartment and that o...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Rogers LK,Valentine CJ,Szczpyka M,Smith CV

    更新日期:2000-09-01 00:00:00

  • Inhibition of skeletal sarcoplasmic reticulum Ca2+-ATPase activity by deferoxamine nitroxide free radical.

    abstract::Deferoxamine is an inhibitor of iron-dependent free radical reactions. Despite the antioxidant roles, prolonged clinical use of the chelator is far from benign, and paradoxically, deferoxamine has been shown to promote lipid peroxidation. The possible toxicity of the drug's metabolites, such as deferoxamine nitroxide ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Kiyose M,Lee CI,Okabe E

    更新日期:1999-02-01 00:00:00

  • Measurement of oxidative damage at pyrimidine bases in gamma-irradiated DNA.

    abstract::Oxidized nucleobases represent one of the main classes of damage induced in DNA by ionizing radiation. Emphasis was placed in this work on the measurement of four oxidized pyrimidine bases, including 5-(hydroxymethyl)uracil (5-HMUra), 5-formyluracil (5-ForUra), 5-hydroxycytosine (5-OHCyt), and 5-hydroxyuracil (5-OHUra...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Douki T,Delatour T,Paganon F,Cadet J

    更新日期:1996-10-01 00:00:00

  • A slipped replication intermediate model is stabilized by the syn orientation of N-2-aminofluorene- and N-2-(acetyl)aminofluorene-modified guanine at a mutational hotspot.

    abstract::The Escherichia coli NarI restriction enzyme recognition site 5'G1G2C3G4C5C63' is a mutational hotspot for -2 deletions in E. coli plasmid pBR322, resulting in the sequence 5'GGCC3' when G4 is modified by the aromatic amine N-2-(acetyl)aminofluorene (AAF) [Burnouf, D., Koehl, P., and Fuchs, R. P. P. (1995) Proc. Natl....

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Roy D,Hingerty BE,Shapiro R,Broyde S

    更新日期:1998-11-01 00:00:00

  • The mechanism of the peroxynitrite-mediated oxidation of myoglobin in the absence and presence of carbon dioxide.

    abstract::Among the cellular components that can react directly with peroxynitrite in the presence of physiological CO(2) concentrations are sulfur-, selenium-, and metal-containing proteins, in particular hemoproteins. We have previously shown that the reactions of peroxynitrite with oxymyoglobin (MbFeO(2)) and oxyhemoglobin p...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Herold S,Exner M,Boccini F

    更新日期:2003-03-01 00:00:00

  • Bioactivation of lamotrigine in vivo in rat and in vitro in human liver microsomes, hepatocytes, and epidermal keratinocytes: characterization of thioether conjugates by liquid chromatography/mass spectrometry and high field nuclear magnetic resonance spe

    abstract::Previous studies suggested that lamotrigene (LTG) underwent bioactivation to a reactive aryl epoxide intermediate in rats. Nevertheless, definitive structures of these thioether conjugates, which are often needed to substantiate the mechanism of bioactivation and identity of reactive intermediate(s), were not fully es...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Chen H,Grover S,Yu L,Walker G,Mutlib A

    更新日期:2010-01-01 00:00:00

  • Mapping Chemical Respiratory Sensitization: How Useful Are Our Current Computational Tools?

    abstract::Chemical respiratory sensitization is an immunological process that manifests clinically mostly as occupational asthma and is responsible for 1 in 6 cases of adult asthma, although this may be an underestimate of the prevalence, as it is under-diagnosed. Occupational asthma results in unemployment for roughly one-thir...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Golden E,Maertens M,Hartung T,Maertens A

    更新日期:2020-12-15 00:00:00

  • Oxidation of a dimethylthiourea metabolite by iodine and acidified iodate: N,N'-dimethylaminoiminomethanesulfinic acid (1).

    abstract::The two major metabolites after S-oxygenation of dimethylthiourea (dimethylaminoiminomethane sulfinic acid, DMAIMSA, and dimethylaminoiminomethane sulfonic acid, DMAIMSOA) were synthesized and tested for their reactivities in the presence of mild oxidants, aqueous iodine and acidic iodate. The stoichiometry of the iod...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Otoikhian A,Simoyi RH,Petersen JL

    更新日期:2005-07-01 00:00:00

  • Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the milk of healthy women.

    abstract::An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary hete...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: DeBruin LS,Martos PA,Josephy PD

    更新日期:2001-11-01 00:00:00

  • Ferroptosis: The Greasy Side of Cell Death.

    abstract::Ferroptosis is a form of cell death that requires phospholipid peroxidation and has attracted increased attention, both as a means to eradicate tumors resistant to standard chemotherapy and for its potential contribution to tissue damage such as in ischemia/reperfusion. The center stage taken by phospholipid peroxidat...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审


    authors: Friedmann Angeli JP,Miyamoto S,Schulze A

    更新日期:2019-03-18 00:00:00

  • Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1.

    abstract::The hepatic carcinogen aflatoxin B1 (AFB1) is metabolized in the liver by at least four different P450s, all of which exhibit large interindividual differences in the expression levels. These differences could affect the individual risk of hepatocellular carcinoma (HCC). We investigated the metabolism of AFB1 in a pan...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Kamdem LK,Meineke I,Gödtel-Armbrust U,Brockmöller J,Wojnowski L

    更新日期:2006-04-01 00:00:00

  • Effect of the peroxisome proliferator perfluoro-n-decanoic acid on glucose transport in the isolated perfused rat liver.

    abstract::The perfluorinated carboxylic acid, perfluoro-n-decanoic acid (PFDA), is a known peroxisome proliferator which displays toxicity in rodents. Using a paired-tracer first-pass extraction technique, the effect of PFDA on hepatic glucose transport was determined in the isolated perfused rat liver. In brief, livers isolate...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Goecke-Flora CM,Wyman JF,Jarnot BM,Reo NV

    更新日期:1995-01-01 00:00:00

  • Cytochrome P450 2A5 constitutive expression and induction by heavy metals is dependent on redox-sensitive transcription factor Nrf2 in liver.

    abstract::Mouse cytochrome P450 2A5 (CYP2A5) is upregulated in various pathophysiological liver diseases and induced by structurally variable hepatotoxic chemicals. A putative common feature for all of these conditions is altered cellular redox status. Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor that is p...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lämsä V,Levonen AL,Leinonen H,Ylä-Herttuala S,Yamamoto M,Hakkola J

    更新日期:2010-05-17 00:00:00

  • Reduction of dimethylarsinic acid to the highly toxic dimethylarsinous acid by rats and rat liver cytosol.

    abstract::Dimethylarsinic acid (DMAs(V)), the major urinary metabolite of inorganic arsenic, is weakly cytotoxic, whereas its reduced form, dimethylarsinous acid (DMAs(III)), is highly toxic. Although glutathione S-transferase omega 1 (GSTO1) and arsenic methyltransferase have been shown or thought to catalyze DMAs(V) reduction...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Németi B,Gregus Z

    更新日期:2013-03-18 00:00:00

  • The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme.

    abstract::Inhaled glucocorticoid (GC) therapy is a vital part of the management of chronic asthma. GCs are metabolized by members of the cytochrome P450 3A family in both liver and lung, but the enzymes are differentially expressed. Selective inhibition of one or more P450 3A enzymes could substantially modify target and system...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Murai T,Reilly CA,Ward RM,Yost GS

    更新日期:2010-08-16 00:00:00

  • Assessing the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity.

    abstract::This study was designed to distinguish and evaluate the contribution of reactive metabolite and reactive oxygen species as the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity. The involvement of reactive oxygen species in the mechanism of in vitro cytotoxicity was examined by the addition...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Tabatabaei AR,Thies RL,Abbott FS

    更新日期:1999-04-01 00:00:00

  • Sustained systemic delivery of green tea polyphenols by polymeric implants significantly diminishes benzo[a]pyrene-induced DNA adducts.

    abstract::The polyphenolics in green tea are believed to be the bioactive components. However, poor bioavailability following ingestion limits their efficacy in vivo. In this study, polyphenon E (poly E), a standardized green tea extract, was administered by sustained-release polycaprolactone implants (two, 2-cm implants; 20% d...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Cao P,Vadhanam MV,Spencer WA,Cai J,Gupta RC

    更新日期:2011-06-20 00:00:00

  • Reactive Sulfur Species-Mediated Activation of the Keap1-Nrf2 Pathway by 1,2-Naphthoquinone through Sulfenic Acids Formation under Oxidative Stress.

    abstract::Sulfhydration by a hydrogen sulfide anion and electrophile thiolation by reactive sulfur species (RSS) such as persulfides/polysulfides (e.g., R-S-SH/R-S-Sn-H(R)) are unique reactions in electrophilic signaling. Using 1,2-dihydroxynaphthalene-4-thioacetate (1,2-NQH2-SAc) as a precursor to 1,2-dihydroxynaphthalene-4-th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Shinkai Y,Abiko Y,Ida T,Miura T,Kakehashi H,Ishii I,Nishida M,Sawa T,Akaike T,Kumagai Y

    更新日期:2015-05-18 00:00:00

  • Double-strand breaks from a radical commonly produced by DNA-damaging agents.

    abstract::Double-strand breaks are widely accepted to be the most toxic form of DNA damage. Molecules that produce double-strand breaks via a single chemical event are typically very cytotoxic and far less common than those that form single-strand breaks. It was recently reported that a commonly formed C4'-radical produces doub...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Taverna Porro ML,Greenberg MM

    更新日期:2015-04-20 00:00:00

  • Photoaddition of fluphenazine to nucleophiles in peptides and proteins. Possible cause of immune side effects.

    abstract::By the action of UVA light, fluphenazine reacted with nucleophiles through a mechanism involving defluorination of its trifluoromethyl group, giving rise to carboxylic acid derivatives that were easily detected by electrospray mass spectrometry. This photoreaction took place with alcohols, sulphydryls, and amines. Whe...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Caffieri S,Miolo G,Seraglia R,Dalzoppo D,Toma FM,van Henegouwen GM

    更新日期:2007-10-01 00:00:00

  • A comparison of the covalent binding of clozapine, procainamide, and vesnarinone to human neutrophils in vitro and rat tissues in vitro and in vivo.

    abstract::Covalent binding of drug reactive metabolites to neutrophils or their precursors is thought to play a role in the development of drug-induced agranulocytosis. In this study, we used immunochemical techniques to compare the covalent binding of clozapine, vesnarinone, and procainamide (three drugs associated with agranu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Gardner I,Popović M,Zahid N,Uetrecht JP

    更新日期:2005-09-01 00:00:00