Effect of deuterium substitution on the disposition of intraperitoneal tryptamine.

Abstract:

:To determine whether alpha,alpha-dideutero substitution in the side chain of the tryptamine molecule can exert primary isotope effects and enhance its bioavailability, equimolar mixtures of tryptamine (T) and either alpha,alpha-dideutero-tryptamine (alpha,alpha-[2H2]T) or beta,beta-dideutero-tryptamine (beta,beta-[2H2]T) were injected i.p. into rats. The amounts of these amines in the brain, liver and plasma were then measured at various times following the injection, and ratios between the deuterated T and T were computed. The ratio remained close to unity in plasma, but exceeded unity in the liver and brain when alpha,alpha-[2H2]T and T were injected; however, when beta,beta-[2H2]T and T were injected, the ratios were unity in all cases at all times. In the presence of a monoamine oxidase inhibitor, the relative enrichment of alpha,alpha-[2H2]T compared to T was reduced. It is concluded that alpha,alpha-dideutero substitution exerts a primary isotope effect during oxidative deamination so that much more of this amine penetrates into, and persists in, the brain.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Dyck LE,Boulton AA

doi

10.1016/0006-2952(86)90482-x

subject

Has Abstract

pub_date

1986-09-01 00:00:00

pages

2893-6

issue

17

eissn

0006-2952

issn

1873-2968

pii

0006-2952(86)90482-X

journal_volume

35

pub_type

杂志文章
  • 2-Bromoethylamine as a potent selective suicide inhibitor for semicarbazide-sensitive amine oxidase.

    abstract::Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of methylamine and aminoacetone to produce toxic aldehydes, i.e. formaldehyde and methylglyoxal, as well as hydrogen peroxide and ammonia. An increase of SSAO activity was detected by different laboratories in patients suffering from vascular disor...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(01)00524-x

    authors: Yu PH,Davis BA,Deng Y

    更新日期:2001-03-15 00:00:00

  • Nonequilibrium modulation of 35S-TBPS binding by benzodiazepine agonists and antagonists.

    abstract::Specific binding of 35S-t-butylbicyclophosphorothionate (TBPS) was studied in synaptosomal membranes of rat cerebral cortex under nonequilibrium conditions. TBPS binding proved to be suitable for the characterization of not only the efficacy but also the potency of benzodiazepine (BZ) receptor ligands in vitro. Five B...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90581-3

    authors: Maksay G,Simonyi M

    更新日期:1988-06-01 00:00:00

  • Increased Akt protein expression is associated with decreased ceramide content in skeletal muscle of troglitazone-treated mice.

    abstract::Although it is generally believed that thiazolidinediones ameliorate insulin resistance by lowering circulating free fatty acids, direct effects of these drugs in skeletal muscle may also contribute to their antidiabetic action. We report that troglitazone administration to mice for 1 day increased the protein express...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2005.01.015

    authors: Planavila A,Alegret M,Sánchez RM,Rodríguez-Calvo R,Laguna JC,Vázquez-Carrera M

    更新日期:2005-04-15 00:00:00

  • Changes in the biliary excretion of organic anions following exhaustive exercise in rats.

    abstract::The effect of exhaustive exercise on the hepatobiliary transport of organic anions was investigated in rats. Animals were run on a rodent treadmill at 24 m/min up a 12% grade (152 +/- 15 min). Exercise resulted in significant hypoglycaemia (-46%) and increased plasma levels of lactate (+12%), together with a marked re...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(90)90094-2

    authors: Villa JG,Collado PS,Almar MM,Gonzalez J

    更新日期:1990-12-01 00:00:00

  • Enhanced DNA excision repair in CCRF-CEM cells resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea, quantitated using the single cell gel electrophoresis (Comet) assay.

    abstract::Enhanced DNA repair activity is important for the development of cellular resistance to alkylating agents. Here, we quantitated the kinetics of DNA excision repairs initiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in human leukemia CCRF-CEM cells. CEM cells that had been established resistant to BCNU (CEM-R) w...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(03)00412-x

    authors: Yamauchi T,Kawai Y,Ueda T

    更新日期:2003-09-15 00:00:00

  • Intracellular glutathione as a determinant of responsiveness to antitumor drugs.

    abstract::The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfox...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90430-2

    authors: Romine MT,Kessel D

    更新日期:1986-10-01 00:00:00

  • Inhibition of the bioenergetic functions of isolated rat liver mitochondria by polyamines.

    abstract::The abilities of the naturally occurring polyamines, putrescine, spermidine and spermine, to affect variables related to the bioenergetic functions of isolated rat liver mitochondria were studied. At concentrations comparable to those present intracellularly, the polyamines inhibited state 4 respiration, but they had ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90654-2

    authors: Byczkowski JZ,Zychlinski L,Porter CW

    更新日期:1982-12-15 00:00:00

  • Reduced (+/-)-3,4-methylenedioxymethamphetamine ("Ecstasy") metabolism with cytochrome P450 2D6 inhibitors and pharmacogenetic variants in vitro.

    abstract::"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine or MDMA] is a CNS stimulant, whose use is increasing despite evidence of long-term neurotoxicity. In vitro, the majority of MDMA is demethylenated to (+/-)-3,4-dihydroxymethamphetamine (DHMA) by the polymorphic cytochrome P450 2D6 (CYP2D6). We investigated the demethy...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(02)01028-6

    authors: Ramamoorthy Y,Yu AM,Suh N,Haining RL,Tyndale RF,Sellers EM

    更新日期:2002-06-15 00:00:00

  • Differential expression of renal adenosine A(1) receptors induced by acute renal failure.

    abstract::The distribution of renal adenosine A(1) receptors was investigated in rats with glycerol- or mercuric chloride (HgCl(2))-induced acute renal failure. Receptors were localised by autoradiography using [(3)H]8-cyclopentyl-1,3-dipropylxanthine ([(3)H]DPCPX), a selective A(1) adenosine receptor antagonist. In saline-inje...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(99)00369-x

    authors: Smith JA,Whitaker EM,Bowmer CJ,Yates MS

    更新日期:2000-03-15 00:00:00

  • Cytotoxicity of BMS-181174. Effects of hypoxia, dicoumarol, and repair deficits.

    abstract::The mitomycin C (MC) analog BMS-181174 (previously designated as BMY25067) has been shown to be active against a variety of solid tumors in mice. The activity of this compound against tumor cell lines resistant to MC and the different toxicity profiles of BMS-181174 and MC suggested that there may be significant diffe...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(95)00264-z

    authors: Rockwell S,Kemple B,Kelley M

    更新日期:1995-10-12 00:00:00

  • Role of CYP2A5 and 2G1 in acetaminophen metabolism and toxicity in the olfactory mucosa of the Cyp1a2(-/-) mouse.

    abstract::Acetaminophen (AP) is a widely-used analgesic agent that has been linked to human liver and kidney disease with prolonged or high-dose usage. In rodents, the target organs that are affected include liver, kidney, and the olfactory mucosa. AP toxicity requires cytochrome P450(CYP)-mediated metabolic activation, and the...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(98)00004-5

    authors: Genter MB,Liang HC,Gu J,Ding X,Negishi M,McKinnon RA,Nebert DW

    更新日期:1998-06-01 00:00:00

  • Effects of methotrexate on purine and pyrimidine metabolism and cell-kinetic parameters in human malignant lymphoblasts of different lineages.

    abstract::MOLT-4 (T-), RAJI (B-), and KM-3 (non-B-non-T-, common ALL) malignant lymphoblasts demonstrated significant differences in their activities of purine de novo synthesis (PDNS) and purine salvage pathway and in their cell-kinetic parameters. Incubations with concentrations of methotrexate (0.02 and 0.2 microM), which ca...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90359-0

    authors: Bökkerink JP,De Abreu RA,Bakker MA,Hulscher TW,van Baal JM,Schretlen ED,De Bruijn CH

    更新日期:1988-06-15 00:00:00

  • Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by phenolic (3E)-4-(2-hydroxyphenyl)but-3-en-2-one in RAW 264.7 macrophages.

    abstract::The large amount of nitric oxide (NO) produced by inducible NO synthase (iNOS) contributes to cellular injury in inflammatory disease. In the present study, a novel synthetic compound (3E)-4-(2-hydroxyphenyl)but-3-en-2-one (HPB) was found to inhibit lipopolysaccharide (LPS)-induced NO generation, but not through the i...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2005.05.032

    authors: Tsao LT,Tsai PS,Lin RH,Huang LJ,Kuo SC,Wang JP

    更新日期:2005-08-15 00:00:00

  • The effect of metformin in EML4-ALK+ lung cancer alone and in combination with crizotinib in cell and rodent models.

    abstract::Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance. We therefore tested metformin alone and in combination with crizotinib in vivo, by...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2020.114345

    authors: Bland AR,Shrestha N,Bower RL,Rosengren RJ,Ashton JC

    更新日期:2021-01-01 00:00:00

  • Effect of diethyl maleate on the biliary excretion rate of infused sulfobromophthalein-glutathione.

    abstract::Diethyl maleate (DEM) was given intraperitoneally to rats in a dose (4.3 mmoles/kg) known to markedly decrease glutathione levels in liver. DEM induced a choleresis previously shown to be due to the osmotic activity of DEM conjugates (DEM-glutathione and subsequent metabolic products) excreted into bile. Coincident wi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90716-x

    authors: Combes B,Backof B

    更新日期:1982-08-15 00:00:00

  • Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression.

    abstract::Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2016.09.022

    authors: Ko JC,Zheng HY,Chen WC,Peng YS,Wu CH,Wei CL,Chen JC,Lin YW

    更新日期:2016-12-15 00:00:00

  • Identification of dual mTORC1 and mTORC2 inhibitors in melanoma cells: prodigiosin vs. obatoclax.

    abstract::The PI3K/AKT/mTOR signaling pathway regulates cell proliferation, survival and angiogenesis. The mammalian target of rapamycin (mTOR) is a protein kinase ubiquitously expressed within cells that regulates cell growth and survival by integrating nutrient and hormonal signals. mTOR exists in two complexes, mTORC1 and mT...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2011.11.027

    authors: Espona-Fiedler M,Soto-Cerrato V,Hosseini A,Lizcano JM,Guallar V,Quesada R,Gao T,Pérez-Tomás R

    更新日期:2012-02-15 00:00:00

  • Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model.

    abstract::Inflammation is a multi-staged process whose expansive phase is thought to be driven by acutely released arachidonic acid (AA) and its metabolites. Inhibition of cyclooxygenase (COX), lipoxygenase (LOX), or soluble epoxide hydrolase (sEH) is known to be anti-inflammatory. Inhibition of sEH stabilizes the cytochrome P4...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2009.10.025

    authors: Liu JY,Yang J,Inceoglu B,Qiu H,Ulu A,Hwang SH,Chiamvimonvat N,Hammock BD

    更新日期:2010-03-15 00:00:00

  • The in vitro ketone reduction of warfarin and analogues. Substrate stereoselectivity, product stereoselectivity and species differences.

    abstract::The in vitro metabolic ketone reduction of warfarin and its 4'-analogues acenocoumarol (4'-nitrowarfarin) and 4'-chlorowarfarin has been investigated using microsomal and cytosolic fractions of several species. Both subcellular fractions showed ketone reductase activity. The cytosolic fractions, in most species, exhib...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90635-7

    authors: Hermans JJ,Thijssen HH

    更新日期:1989-10-01 00:00:00

  • Acetaminophen-induced stimulation of MDR1 expression and activity in rat intestine and in LS 174T human intestinal cell line.

    abstract::The well-known analgesic and antipyretic drug N-acetyl-p-aminophenol (acetaminophen; APAP) has been previously reported to affect MDR1 expression in rat liver. In this study, we have investigated the effect of subtoxic doses of APAP on MDR1 expression and activity in rat intestine and human intestinal cells. Administr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2010.10.006

    authors: Ghanem CI,Arias A,Novak A,Carpini GD,Villanueva S,Blazquez AG,Marin JJ,Mottino AD,Rubio MC

    更新日期:2011-01-15 00:00:00

  • Nitroblue tetrazolium inhibits oxidation of glyceryl trinitrate to nitric oxide in bovine aortic smooth muscle cells.

    abstract::The effects of nitroblue tetrazolium (NBT), a well-known scavenger of superoxide anions and an inhibitor of nicotinamide adenine dinucleotide (NADPH)-dependent oxidations, were assessed on the metabolism of glyceryl trinitrate (GTN) to nitric oxide (NO) by bovine aortic smooth muscle cells (SMC). The extent of this me...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90300-x

    authors: Pistelli A,Mollace V,Nistico G,Salvemini D,Vane J

    更新日期:1994-05-18 00:00:00

  • Zinc effects on glutathione metabolism relationship to zinc-induced protection from alkylating agents.

    abstract::Several aspects of the effects of zinc on the metabolism of glutathione were examined in the Chinese hamster cell (line CHO) and in three derived sublines which differ in their resistance to the thiol reactive heavy metal cadmium. In the parental CHO cell, which does not induce the synthesis of metallothionein in resp...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(83)90243-5

    authors: Seagrave J,Tobey RA,Hildebrand CE

    更新日期:1983-10-15 00:00:00

  • Reversal of antigen-dependent signaling by two mutations in antibody/receptor chimera: implication of inverse agonism in cytokine receptor superfamily.

    abstract::Understanding the receptor activation mechanism is essential for the rational design of pharmacologically active ligand molecules. However, the activation mechanism of most cytokine receptors remains still unclear, and while agonism and antagonism have been described for ligand-mimetic peptides, there has been no repo...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2004.04.014

    authors: Kawahara M,Ishii S,Tsumoto K,Kumagai I,Ueda H,Nagamune T

    更新日期:2004-08-01 00:00:00

  • Alcohol abuse increases the lipid structural order in human erythrocyte membranes. A steady-state and time-resolved anisotropy study.

    abstract::The effect of ethanol abuse on the lipid ordering of the human erythrocyte membranes was studied by steady-state and time-resolved fluorescence anisotropy measurements of DPH and its polar analogue TMA-DPH, which probe different membrane regions. Steady-state anisotropy values with DPH as a probe were slightly but sig...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90062-7

    authors: Beaugé F,Gallay J,Stibler H,Borg S

    更新日期:1988-10-15 00:00:00

  • Role of cytochrome P450 1A2 in bilirubin degradation Studies in Cyp1a2 (-/-) mutant mice.

    abstract::In congenital jaundice, which is due to defects of bilirubin gluruconidation, bilirubin is degraded by an alternative pathway into unidentified products. Previously, it was shown that plasma bilirubin levels can be decreased in rats with this defect by inducers of CYP1A enzymes. Here, liver microsomes from rats or mic...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(01)00568-8

    authors: Zaccaro C,Sweitzer S,Pipino S,Gorman N,Sinclair PR,Sinclair JF,Nebert DW,De Matteis F

    更新日期:2001-04-01 00:00:00

  • The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice.

    abstract::The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E fe...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(96)00869-6

    authors: Yano T,Yano Y,Uchida M,Murakami A,Hagiwara K,Otani S,Ichikawa T

    更新日期:1997-06-01 00:00:00

  • Effect of stereo and regiochemistry towards wild and multidrug resistant HIV-1 virus: viral potency of chiral PETT derivatives.

    abstract::Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme of the human immunodeficiency virus (HIV-1). Molecular modeling studies indicated that because of the asymmetric geometry of the non-nucleoside inhib...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2004.01.019

    authors: Venkatachalam TK,Mao C,Uckun FM

    更新日期:2004-05-15 00:00:00

  • Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate and species differences in response.

    abstract::Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate (DEHA) has been achieved using primary hepatocyte cultures derived from different species and cyanide-insensitive fatty acyl CoA oxidase (PCO) as a marker enzyme for peroxisome proliferation. In rat and mouse hepatocytes,...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(92)90171-e

    authors: Cornu MC,Lhuguenot JC,Brady AM,Moore R,Elcombe CR

    更新日期:1992-05-28 00:00:00

  • Effects of hypophysectomy and thyroxine on the expression of hepatic oestrogen, hydroxysteroid and phenol sulphotransferases.

    abstract::Sulphation in rats, and other mammals, is carried out by a family of sulphotransferase isoenzymes, which can be further subdivided into oestrogen, hydroxysteroid and phenol sulphotransferases. We have examined the effects of hypophysectomy on the activity and expression of representative members of the three major sul...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(95)00055-5

    authors: Borthwick EB,Voice MW,Burchell A,Coughtrie MW

    更新日期:1995-05-17 00:00:00

  • Evidence against involvement of calcium in carbon tetrachloride-dependent inhibition of lipid secretion by isolated hepatocytes.

    abstract::Carbon tetrachloride (CCl4)-induced inhibition of very low density lipoprotein (VLDL) secretion was studied in isolated hepatocytes. The hypothesis that inhibition of secretion is due to altered calcium homeostasis following CCl4-dependent inhibition of endoplasmic reticulum calcium sequestration was investigated. Inh...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90714-7

    authors: Pencil SD,Brattin WJ Jr,Glende EA Jr,Recknagel RO

    更新日期:1984-08-01 00:00:00