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












  • Glutathione Conjugation and Protein Adduction by Environmental Pollutant 2,4-Dichlorophenol In Vitro and In Vivo.

    abstract::2,4-Dichlorophenol (2,4-DCP), an environmental pollutant, was reported to cause hepatotoxicity. The biochemical mechanisms of 2,4-DCP induced liver injury remain unknown. The present study showed that 2,4-DCP is chemically reactive and spontaneously reacts with GSH and bovine serum albumin to form GSH conjugates and B...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Li Q,Li W,Zhao J,Guo X,Zou Q,Yang Z,Tian R,Peng Y,Zheng J

    更新日期:2020-09-21 00:00:00

  • Common E-Cigarette Flavoring Chemicals Impair Neutrophil Phagocytosis and Oxidative Burst.

    abstract::E-cigarette flavorings have not been thoroughly evaluated for inhalational toxicity. We have shown that the flavoring chemical cinnamaldehyde impairs human neutrophils, macrophages, and natural killer cells. Here we investigated the effects of other common e-liquid flavoring chemicals on phagocytosis and oxidative bur...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Hickman E,Herrera CA,Jaspers I

    更新日期:2019-06-17 00:00:00

  • Alkylation of 2'-deoxynucleosides and DNA by the Premarin metabolite 4-hydroxyequilenin semiquinone radical.

    abstract::Premarin (Wyeth-Ayerst) is the estrogen replacement treatment of choice and continues to be one of the most widely dispensed prescriptions in the United States. In addition to endogenous estrogens, Premarin contains unsaturated estrogens including equilenin. We synthesized the catechol metabolite of equilenin, 4-hydro...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Shen L,Qiu S,Chen Y,Zhang F,van Breemen RB,Nikolic D,Bolton JL

    更新日期:1998-02-01 00:00:00

  • In Vitro Method to Quantify Dermal Absorption of Pesticide Residues.

    abstract::All pesticides must go through a rigorous risk assessment process in order to show that they are safe for use.With respect to dermal risk assessment for re-entry workers, the absorption value applied to predict systemic dose from this external exposure is obtained by testing liquid forms of the pesticide in vivo and/o...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Clarke JF,Cordery SF,Morgan NA,Knowles PK,Guy RH

    更新日期:2015-02-16 00:00:00

  • Enhancing Bulge Stabilization through Linear Extension of C8-Aryl-Guanine Adducts to Promote Polymerase Blockage or Strand Realignment to Produce a C:C Mismatch.

    abstract::Aryl radicals can react at the C8-site of 2'-deoxyguanosine (dG) to produce DNA adducts with a C8-C linkage (denoted C-linked). Such adducts are structurally distinct from those possessing a flexible amine (N-linked) or ether (O-linked) linkage, which separates the C8-aryl moiety from the guanine nucleobase. In the cu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Sproviero M,Verwey AM,Witham AA,Manderville RA,Sharma P,Wetmore SD

    更新日期:2015-08-17 00:00:00

  • Nitration of Tyrosine Residue Y10 of Aβ1-42 Significantly Inhibits Its Aggregation and Cytotoxicity.

    abstract::Amyloid-β plaques and oxidative stress are the major hallmarks of Alzheimer's disease. Our previous study found that the heme-Aβ complex enhanced the catalytic effect of free heme on protein tyrosine nitration in the presence of hydrogen peroxide (H2O2) and nitrite (NO2-). Y10 in Aβ could be the first target to be nit...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Zhao J,Wu J,Yang Z,Li H,Gao Z

    更新日期:2017-04-17 00:00:00

  • Copper-2 Hypothesis for Causation of the Current Alzheimer's Disease Epidemic Together with Dietary Changes That Enhance the Epidemic.

    abstract::Alzheimer's disease, the most common cause of dementia, is at epidemic proportions (15 to 44% depending on age, of those age 65 to 84) in the U.S. and other developed countries but remains relatively rare in undeveloped countries. Surprisingly, solid historical data reveal the epidemic is a creature of the last centur...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审


    authors: Brewer GJ

    更新日期:2017-03-20 00:00:00

  • Carbon Disulfide Induces Embryo Implantation Disorder by Disturbing the Polarization of Macrophages in Mice Uteri.

    abstract::Carbon disulfide (CS2) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Zhang T,Hu C,Wu Y,Wang S,Liu X,Zhang D,Huang F,Gao H,Wang Z

    更新日期:2019-10-21 00:00:00

  • Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease.

    abstract::The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells. The in vi...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Casida JE,Ford B,Jinsmaa Y,Sullivan P,Cooney A,Goldstein DS

    更新日期:2014-08-18 00:00:00

  • Selective inhibition of cytochrome P450 2E1 in vivo and in vitro with trans-1,2-dichloroethylene.

    abstract::The effect of trans-1,2-dichloroethylene (DCE), an inhibitor of cytochrome P450 (P450) 2E1, on the catalytic activities and total content of hepatic P450 was determined in vivo and in vitro. Hepatic microsomes were prepared from groups of rats prior to dosing and at 2, 5, 12, and 24 h postdosing, and total P450 conten...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Mathews JM,Etheridge AS,Raymer JH,Black SR,Pulliam DW Jr,Bucher JR

    更新日期:1998-07-01 00:00:00

  • Caenorhabditis elegans Model Studies Show MPP+ Is a Simple Member of a Large Group of Related Potent Dopaminergic Toxins.

    abstract::Although the causes of Parkinson's disease (PD) are not fully understood, the consensus is that a combination of genetic and environmental factors plays a major role. The discovery that the synthetic chemical, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-derived N-methyl-4-phenylpyridinium (MPP+), recapitulates...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Murphy D,Patel H,Wimalasena K

    更新日期:2021-01-26 00:00:00

  • Intersection of the Roles of Cytochrome P450 Enzymes with Xenobiotic and Endogenous Substrates: Relevance to Toxicity and Drug Interactions.

    abstract::Today much is known about cytochrome P450 (P450) enzymes and their catalytic specificity, but the range of reactions catalyzed by each still continues to surprise. Historically, P450s had been considered to be involved in either the metabolism of xenobiotics or endogenous chemicals, in the former case playing a genera...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Guengerich FP

    更新日期:2017-01-17 00:00:00

  • Particulate depleted uranium is cytotoxic and clastogenic to human lung cells.

    abstract::Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and non-combatants is potentially frequent and widespread. DU is considered a suspected human carcinogen, affecting the bronchial cells of the lung. However, few investigations have studied DU in human bronchial cell...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Wise SS,Thompson WD,Aboueissa AM,Mason MD,Wise JP Sr

    更新日期:2007-05-01 00:00:00

  • Water-soluble organotellurium compounds: catalytic protection against peroxynitrite and release of zinc from metallothionein.

    abstract::The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc st...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Jacob C,Arteel GE,Kanda T,Engman L,Sies H

    更新日期:2000-01-01 00:00:00

  • DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland carcinogen, catalyzed by rat liver or mammary gland cytosol.

    abstract::Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O-esterification. This study analyzes the DNA binding and adducts from the in vitro nitrored...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Ritter CL,Culp SJ,Freeman JP,Marques MM,Beland FA,Malejka-Giganti D

    更新日期:2002-04-01 00:00:00

  • Studies on the adduct heterogeneity of benzo[a]pyrene 7, 8-dihydrodiol 9,10-epoxide stereoisomers covalently bound to deoxyribooligonucleotides by induced circular dichroism and light absorption spectroscopy.

    abstract::The binding conformations of single anti- and syn-BPDE-N2-dG adducts in oligonucleotides of varying base composition have been studied by induced circular dichroism (ICD) and light absorption spectroscopy. The sign of the ICD in single-stranded oligonucleotide adducts correlates with the absolute configuration of the ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Pradhan P,Jernström B,Seidel A,Nordén B,Gräslund A

    更新日期:1999-05-01 00:00:00

  • Microsomal catalyzed N-hydroxylation of guanabenz and reduction of the N-hydroxylated metabolite: characterization of the two reactions and genotoxic potential of guanoxabenz.

    abstract::The N-reduction of the centrally acting alpha 2-adrenoreceptor agonist guanoxabenz (Benzérial), an N-hydroxyamidinohydrazone, to the amidinohydrazone guanabenz (Wytensin, Hipten, Rexitene) by microsomal fractions from rabbits, pigs and humans has been detected in vitro. The conversion rates with rabbit microsomal frac...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Clement B,Demesmaeker M,Linne S

    更新日期:1996-06-01 00:00:00

  • Inhibition of topoisomerase I function by nitidine and fagaronine.

    abstract::The benzophenanthridine alkaloids nitidine and fagaronine were characterized as inhibitors of topoisomerase I function. In common with the antitumor agent camptothecin, both nitidine and fagaronine stabilized the covalent binary complex formed between calf thymus topoisomerase I and DNA. The effects of these compounds...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Wang LK,Johnson RK,Hecht SM

    更新日期:1993-11-01 00:00:00

  • Cytochrome P450 2A-catalyzed metabolic activation of structurally similar carcinogenic nitrosamines: N'-nitrosonornicotine enantiomers, N-nitrosopiperidine, and N-nitrosopyrrolidine.

    abstract::N'-Nitrosonornicotine (NNN) and N-nitrosopiperidine (NPIP) are potent esophageal and nasal cavity carcinogens in rats and pulmonary carcinogens in mice. N-Nitrosopyrrolidine (NPYR) induces mainly liver tumors in rats and is a weak pulmonary carcinogen in mice. These nitrosamines may be causative agents in human cancer...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Wong HL,Murphy SE,Hecht SS

    更新日期:2005-01-01 00:00:00

  • Acrylamide Induces Senescence in Macrophages through a Process Involving ATF3, ROS, p38/JNK, and a Telomerase-Independent Pathway.

    abstract::Senescence, which is irreversible cell cycle arrest, is induced by various types of DNA damage, including genotoxic stress. Senescent cells show dysregulation of tumor suppressor genes and other regulators of cellular proliferation. Activating transcription factor 3 (ATF3) plays a pleiotropic role in biological proces...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Kim KH,Park B,Rhee DK,Pyo S

    更新日期:2015-01-20 00:00:00

  • Microsomal biotransformation of benzo[ghi]perylene, a mutagenic polycyclic aromatic hydrocarbon without a "classic" bay region.

    abstract::Carcinogenic polycyclic aromatic hydrocarbons (PAH), e.g., benzo[a]pyrene (BaP), possess a bay region comprising an ortho-fused benzene ring. Benzo[ghi]perylene (BghiP) represents the group of PAHs lacking such a "classic" bay region and hence cannot be metabolically converted like BaP to bay region dihydrodiol epoxid...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Platt KL,Grupe S

    更新日期:2005-04-01 00:00:00

  • Efficient synthesis of the benzo[a]pyrene metabolic adducts of 2'-deoxyguanosine and 2'-deoxyadenosine and their direct incorporation into DNA.

    abstract::A new and efficient method is described for the synthesis in gram quantities of the benzo[a]pyrene (B[a]P) metabolic adducts of 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) substituted, respectively, at the N(2)- and N(6)- positions. When the racemic form of the tris(benzoyloxy)amine 5 (related to the notoriously...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Johnson F,Bonala R,Tawde D,Torres MC,Iden CR

    更新日期:2002-12-01 00:00:00

  • A Multiplatform Approach for the Discovery of Novel Drug-Induced Kidney Injury Biomarkers.

    abstract::Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrated the use of label-free liquid chromatography-mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety bioma...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Chen L,Smith J,Mikl J,Fryer R,Pack F,Williams BJ,Phillips JA,Papov VV Jr

    更新日期:2017-10-16 00:00:00

  • Glutathione and N-acetylcysteine conjugates of 2-chloroethyl isocyanate. Identification as metabolites of N,N'-bis(2-chloroethyl)-N-nitrosourea in the rat and inhibitory properties toward glutathione reductase in vitro.

    abstract::The antitumor agent N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) is known to be unstable in aqueous solution, and to degrade spontaneously to reactive alkylating and carbamoylating intermediates. Whereas the alkylating component is believed to be responsible for the antitumor effects of this drug, it has been speculat...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Davis MR,Kassahun K,Jochheim CM,Brandt KM,Baillie TA

    更新日期:1993-05-01 00:00:00

  • Caffeine-derived N-nitroso compounds. II. Synthesis and characterization of nitrosation products from caffeidine and caffeidine acid.

    abstract::Caffeine on alkaline hydrolysis produces caffeidine [1-methyl-4-(methylamino)-5-(N-methylcarbamoyl)imidazole] and caffeidine acid [N-[4-(5-carboxy-1-methylimidazolyl)]-N,N'-dimethylurea]. We now report the synthesis and chemical characterization of mononitrosocaffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5-(N-methy...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Kumar R,Wacker CD,Mende P,Spiegelhalder B,Preussmann R,Siddiqi M

    更新日期:1993-01-01 00:00:00

  • Mechanism of the N-hydroxylation of primary and secondary amines by cytochrome P450.

    abstract::Cytochrome P450 enzymes (CYPs) metabolize alkyl- and arylamines, generating several different products. For the primary and secondary amines, some of these reactions result in hydroxylated amines, which may be toxic. Thus, when designing new drugs containing amine groups, it is important to be able to predict if a giv...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Seger ST,Rydberg P,Olsen L

    更新日期:2015-04-20 00:00:00

  • Abiotic sulfhydryl reactivity: a predictor of aquatic toxicity for carbonyl-containing alpha,beta-unsaturated compounds.

    abstract::A diverse series of aliphatic alpha,beta-unsaturated esters, ketones, and aldehydes were evaluated for reactivity with the model nucleophile sulfhydryl group in the form of the cysteine residue of the tripeptide glutathione; the reactive end point (RC50) was then related to aquatic toxicity (IGC50) assessed in the Tet...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yarbrough JW,Schultz TW

    更新日期:2007-03-01 00:00:00

  • Hypochlorite-induced damage to DNA, RNA, and polynucleotides: formation of chloramines and nitrogen-centered radicals.

    abstract::Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal agent, but can also damage host tissue. As there is a strong link between chronic inflammation and some cancers, we have investigated HOCl damage to DNA, RNA...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Hawkins CL,Davies MJ

    更新日期:2002-01-01 00:00:00

  • Bioactivation of lumiracoxib by peroxidases and human liver microsomes: identification of multiple quinone imine intermediates and GSH adducts.

    abstract::Lumiracoxib (Prexige; 2-[(2-fluoro-6-chlorophenyl)amino]-5-methyl-benzeneacetic acid) is a cyclooxygenase-2 selective inhibitor for the symptomatic treatment of osteoarthritis. Recently, the drug has been withdrawn in several countries due to serious liver side effects. Li et al. recently have shown that lumiracoxib i...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Kang P,Dalvie D,Smith E,Renner M

    更新日期:2009-01-01 00:00:00

  • Comparison of rates of enzymatic oxidation of aflatoxin B1, aflatoxin G1, and sterigmatocystin and activities of the epoxides in forming guanyl-N7 adducts and inducing different genetic responses.

    abstract::The genotoxicity of the dihydrofurans aflatoxin B1 (AFB1), aflatoxin G1 (AFG1), and sterigmatocystin (STG) was examined in a bacterial system in which the induction of SOS repair is monitored with the umuC gene linked to a lacZ reporter gene in plasmid pSK1002. Human liver microsomal cytochrome P-450NF oxidized the di...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Baertschi SW,Raney KD,Shimada T,Harris TM,Guengerich FP

    更新日期:1989-03-01 00:00:00