Bibliographies thématiques / Carboxylic acids Metabolism

Littérature scientifique sur le sujet « Carboxylic acids Metabolism »

Auteur : Grafiati

Publié le 4 juin 2021

Mis à jour le 1 février 2022

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Articles de revues sur le sujet "Carboxylic acids Metabolism"

Iwami, Y., S. Hata, N. Takahashi et T. Yamada. « Difference in Amounts between Titratable Acid and Total Carboxylic Acids Produced by Oral Streptococci during Sugar Metabolism ». Journal of Dental Research 68, n^o 1 (janvier 1989) : 16–19. http://dx.doi.org/10.1177/00220345890680010101.

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The acid produced by the resting cells of Streptococcus mutans NCTC 10449 and HS 6 and S. sanguis ATCC 10556 during sugar metabolism was estimated with a pH-stat and a carboxylic acid analyzer. Lactic, formic, acetic, pyruvic, and carbonic acids were detected in the reaction mixtures, but propionic, citric, succinic, iso-butyric, butyric, iso-valeric, and valeric acids were not detected. The amount of titratable acid estimated by alkaline titration with the pH-stat was larger than the amount of total carboxylic acids estimated with the carboxylic acid analyzer. The difference in quantity between the titratable and the total carboxylic acids increased significantly with an increase in the period of incubation with sugar. Moreover, the value of the alkaline titration of standard lactic, formic, acetic, and pyruvic acids was equal to the amount analyzed with the carboxylic acid analyzer. The results indicated that these two streptococci produced not only these carboxylic acids but also other acid(s), possibly non-carboxylic acid(s), during their sugar metabolism.

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Goyal, R., R. Tardif et J. Brodeur. « Influence of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid, on the urinary elimination of mercapturic acids of ethylene oxide, dibromoethane, and acrylonitrile : a dose–effect study ». Canadian Journal of Physiology and Pharmacology 67, n^o 3 (1 mars 1989) : 207–12. http://dx.doi.org/10.1139/y89-035.

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Metabolic disposition of ethylene oxide, dibromoethane, and acrylonitrile in rats after acute exposure was studied by examining the relationship between dose and urinary metabolites, and by establishing the influence of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the above relationship. Respective urinary metabolites, hydroxyethylmercapturic acid, cyanoethylmercapturic acid, thiocyanate, and ethylene glycol, were quantified to estimate the extent to which each compound was metabolized. The animals were given either ethylene oxide (0.34, 0.68, or 1.36 mmol/kg), dibromoethane (0.2, 0.4, or 0.6 mmol/kg), or acrylonitrile (0.10, 0.38, or 0.76 mmol/kg). Urine samples were collected at 24 h. The metabolic biotransformation of all three chemicals to their respective mercapturic acids was strongly indicative of saturable metabolism. Administration of OTCA (4–5 mmol/kg) enhanced gluthathione availability and increased excretion of urinary mercapturic acids at the higher doses of the chemicals. This study indicates that OTCA increases the capacity for detoxification via the glutathione pathway thereby partially correcting the nonlinearity between the administered dose of ethylene oxide, dibromoethane, and acrylonitrile and the amount of certain urinary metabolites.Key words: ethylene oxide metabolism, dibromoethane metabolism, acrylonitrile metabolism, mercapturic acids, glutathione, cysteine prodrugs, L-2-oxothiazolidine-4-carboxylic acid.

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Sarkar, Omprakash, A. Naresh Kumar, Shikha Dahiya, K. Vamshi Krishna, Dileep Kumar Yeruva et S. Venkata Mohan. « Regulation of acidogenic metabolism towards enhanced short chain fatty acid biosynthesis from waste : metagenomic profiling ». RSC Advances 6, n^o 22 (2016) : 18641–53. http://dx.doi.org/10.1039/c5ra24254a.

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Darnell, Malin, et Lars Weidolf. « Metabolism of Xenobiotic Carboxylic Acids : Focus on Coenzyme A Conjugation, Reactivity, and Interference with Lipid Metabolism ». Chemical Research in Toxicology 26, n^o 8 (5 juillet 2013) : 1139–55. http://dx.doi.org/10.1021/tx400183y.

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Beaulieu, Pierre L., René Coulombe, James Gillard, Christian Brochu, Jianmin Duan, Michel Garneau, Eric Jolicoeur et al. « Allosteric N-acetamide-indole-6-carboxylic acid thumb pocket 1 inhibitors of hepatitis C virus NS5B polymerase — Acylsulfonamides and acylsulfamides as carboxylic acid replacements ». Canadian Journal of Chemistry 91, n^o 1 (janvier 2013) : 66–81. http://dx.doi.org/10.1139/cjc-2012-0319.

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Acylsulfonamide and acylsulfamide as surrogates for the carboxylic acid function of N-acetamide-indole-6-carboxylic acids were evaluated as allosteric inhibitors of hepatitis C virus (HCV) NS5B polymerase. Several analogs displayed excellent antiviral potency against both 1a and 1b HCV genotypes in cell-based subgenomic replicon assays. Structure–activity relationships (SAR) are discussed in the context of the crystal structure of an inhibitor − NS5B polymerase complex. Absorption, distribution, metabolism, and excretion pharmacokinetic (ADME-PK) properties of this class of inhibitors are also described.

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Omran, Arthur, Cesar Menor-Salvan, Greg Springsteen et Matthew Pasek. « The Messy Alkaline Formose Reaction and Its Link to Metabolism ». Life 10, n^o 8 (28 juillet 2020) : 125. http://dx.doi.org/10.3390/life10080125.

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Sugars are essential for the formation of genetic elements such as RNA and as an energy/food source. Thus, the formose reaction, which autocatalytically generates a multitude of sugars from formaldehyde, has been viewed as a potentially important prebiotic source of biomolecules at the origins of life. When analyzing our formose solutions we find that many of the chemical species are simple carboxylic acids, including α-hydroxy acids, associated with metabolism. In this work we posit that the study of the formose reaction, under alkaline conditions and moderate hydrothermal temperatures, should not be solely focused on sugars for genetic materials, but should focus on the origins of metabolism (via metabolic molecules) as well.

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Knights, Kathleen M., Matthew J. Sykes et John O. Miners. « Amino acid conjugation : contribution to the metabolism and toxicity of xenobiotic carboxylic acids ». Expert Opinion on Drug Metabolism & ; Toxicology 3, n^o 2 (avril 2007) : 159–68. http://dx.doi.org/10.1517/17425255.3.2.159.

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Bock, Susanne, Ulrich A. Sedlmeier et Klaus H. Hoffmann. « Metabolism of absorbed short-chain carboxylic acids by the freshwater oligochaete Tubifex tubifex ». Comparative Biochemistry and Physiology Part B : Comparative Biochemistry 92, n^o 1 (janvier 1989) : 35–40. http://dx.doi.org/10.1016/0305-0491(89)90309-x.

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Knights, Kathleen M. « ROLE OF HEPATIC FATTY ACID:COENZYME A LIGASES IN THE METABOLISM OF XENOBIOTIC CARBOXYLIC ACIDS ». Clinical and Experimental Pharmacology and Physiology 25, n^o 10 (octobre 1998) : 776–82. http://dx.doi.org/10.1111/j.1440-1681.1998.tb02152.x.

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Arun, Viswanath, Takashi Mino et Tomonori Matsuo. « Metabolism of Carboxylic Acids Located in and around the Glycolytic Pathway and the TCA Cycle in the Biological Phosphorus Removal Process ». Water Science and Technology 21, n^o 4-5 (1 avril 1989) : 363–74. http://dx.doi.org/10.2166/wst.1989.0238.

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Anaerobic batch experiments were performed to measure the profile of various parameters when phosphorus accumulating sludge acclimatized under anaerobic-aerobic operation is fed with malic, lactic, pyruvic, propionic and succinic acids - carboxylic acids that lie in the vicinity of the Glycolytic pathway and the Tricarboxylic acid cycle - two pathways central to the utilization of organics as sources of energy and carbon in most microorganisms. Carbon dioxide gas produced during substrate uptake was also measured. In most cases, intra-cellular carbohydrate reserves are consumed and the NADH2 that is consequently produced requires that there be some subsequent reaction that utilizes it.

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Thèses sur le sujet "Carboxylic acids Metabolism"

Rocha, Sandra Carla. « Avaliação das perspectivas terapêuticas do ácido L-tiazolidina-4-carboxílico, um análogo de prolina, na infecção de camundongos pelo Trypanosoma cruzi ». Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/42/42135/tde-16082011-160411/.

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Trypanosoma cruzi é dependente de prolina para diversos processos tal como metabolismo energético, invasão celular, diferenciação e resistência a estresse osmótico, metabólico e oxidativo. O ácido L-tiazolidina-4-carboxílico (T4C), um análogo estrutural da prolina, inibe competitivamente o transporte deste aminoácido em T. cruzi, e interage sinergicamente com fatores de estresse que ocorrem ao longo do seu ciclo de vida. Aqui nós avaliamos o efeito de T4C na infecção de camundongos pelo T. cruzi. Foi observada uma redução de 49% do pico parasitêmico de animais infectados e tratados com dose única de T4C (100 mg/Kg). A análise histológica e por PCR quantitativa de diferentes tecidos revelou uma redução significativa da carga parasitária apenas no intestino de animais tratados com T4C (100 ou 150 mg/Kg). Por outro lado, a dose única de 200 mg/Kg diminuiu o peso corporal e sobrevida de animais não infectados. O tratamento prolongado (10 mg/Kg dia) não reduziu a parasitemia, mas aumentou a sobrevida e diminuiu a carga parasitária no intestino. T4C não afetou a expressão gênica de IFN-g e IL-10 em qualquer um dos tecidos analisados (coração, baço, intestino). Em conclusão, T4C contribui em reduzir a virulência da infecção, mas é tóxico em doses que superem 150 mg/kg.
Trypanosoma cruzi is dependent on proline for a variety of processes such as energy metabolism, host cell invasion, differentiation and resistance to osmotic, metabolic and oxidative stress. L-thiazolidine-4-carboxylic acid (T4C), a proline structural analogue, inhibits the proline uptake and interacts with several stress factors that the parasite undergoes throughout its life cycle. Herein, we evaluated the T4C effects on mice infection by T. cruzi. It was observed a reduction of 49% of the parasitemia peak in infected mice that were treated with a unique dose of T4C (100 mg/Kg). Histological and quantitative PCR analysis of several tissues revealed a significant reduction of parasite load in the intestine (100 or 150 mg/kg). In the other hand, the unique dose of 200 mg/Kg reduced the body weight and survival of non-infected mice. A T4C prolonged treatment (10 mg/Kg day), did not diminish the parasitemia, but increased survival and reduced the parasite load in the intestine. T4C did not affect the gene expression of g-IFN and IL-10 in any of the organs analyzed (heart, spleen, intestine). In conclusion, T4C-treatment contributes to reduce the virulence of T. cruzi infection, but it was toxic in doses over 150 mg/kg.

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Li, Chien-Ming. « In Vitro and in Vivo Pharmacology of 4-Substituted Methoxybenzoyl-Aryl-Thiazoles (SMART) and 2-Arylthiazolidine-4-Carboxylic Acid Amides (ATCAA) ». The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1281966183.

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Hermant, Paul. « Les acides hydroxamiques comme molécules bioactives. Conception, synthèse, propriétés pharmacocinétiques et évaluation biologique ». Thesis, Lille 2, 2017. http://www.theses.fr/2017LIL2S021.

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Dans le monde biologique la fonction acide hydroxamique est retrouvée dans les champignons, les levures, les bactéries et les plantes comme agent sidérophore. La propriété des acides hydroxamiques de lier les métaux est exploitée en chimie médicinale dans des stratégies d’inhibition de métalloenzymes à zinc. Ainsi, les acides hydroxamiques sont largement étudiés dans différentes aires thérapeutiques telles qu’en infectiologie, parasitologie, oncologie, cardio-métabolique et dans les maladies inflammatoires. La mise sur le marché d’acides hydroxamiques inhibiteurs des HDACs, tels que le vorinostat et le belinostat dans le traitement de lymphomes cutanés à cellules T atteste de leur potentiel en thérapeutique.Le travail présenté dans cette thèse porte sur la conception et la synthèse d’acides hydroxamiques dans le but d’explorer d’une part leurs propriétés pharmacocinétiques in vitro et in vivo, et d’autre part de développer certains d’entre-eux comme inhibiteurs de l’insulin-degrading enzyme.Après une introduction générale sur les propriétés biologiques des acides hydroxamiques, nous présentons la première étude extensive des relations structure-stabilité plasmatique de ces molécules, réalisée sur une chimiothèque de 57 produits représentant différents pharmacophores. Nous avons mis en évidence des motifs chimiques favorisant ou bloquant l’hydrolyse des acides hydroxamiques dans plusieurs fluides biologiques. De plus, grâce à des inhibiteurs sélectifs d’estérases nous avons mis en exergue les principales estérases impliquées dans l’hydrolyse plasmatique des acides hydroxamiques : les arylestérases et les carboxylestérases. Ces résultats ont été complétés par une étude de modélisation moléculaire des différents acides hydroxamiques substrats des estérases.En parallèle, les propriétés pharmacocinétiques et pharmacodynamiques d’une série d’acides hydroxamiques inhibiteurs de l’insulin-degrading enzyme ont été investiguées via le développement d’une formulation afin d’augmenter l’exposition in vivo au produit et la caractérisation d’interactions ligand-protéine par RMN du fluor. Finalement, nous nous sommes intéressés à la conception et à la synthèse d’acides hydroxamiques macrocycliques. Deux voies synthétiques originales et complémentaires ont été développées. L’une d’entre-elles a permis l’obtention de macrocycles d’une taille comprise entre 24 et 26 chainons
Biologically the hydroxamic acid function is founded in fungus, yeast, bacteria and plant as siderophore agent. This property to bind metals is widely used in medicinal chemistry to develop potent and selective inhibitors of metalloenzymes. Thus, hydroxamic acids are developed in numerous therapeutic areas such as infectiology, parasitology, oncology, cardio-metabolic or inflammatory diseases. The approval of hydroxamic acids inhibitors of HDACs, like vorinostat and belinostat for cutaneous T-cell lymphoma, supports the great therapeutic potential of this kind of molecules.Research exposed in this thesis deals with conception and synthesis of hydroxamic acids to explore on one hand, their in vitro and in vivo pharmacokinetics properties, and on another hand to develop some of them as inhibitors of insulin-degrading enzyme.After a general introduction about the biological properties of hydroxamic acids, we present the first comprehensive structure-plasma stability relationships, using a 57-member library displaying diverse pharmacophores. We have identified the structural motives that favor or block hydrolysis of hydroxamic acids in various biological fluids. Thanks to selective esterase inhibitors, we have evidenced which plasmatic esterases were involved in the hydrolysis of such compounds: arylesterases and carboxylesterases. These results were completed by a molecular modeling study on different hydroxamic acids substrates of these enzymes.Besides, pharmacodynamics and pharmacokinetics properties of hydroxamic acids inhibitors of insulin-degrading enzyme were explored via the development of a 19F NMR ligand-based assay, and the development of a new formulation to enhance the compound’s exposure in vivo. In the last part, we disclose the conception and synthesis of macrocyclic hydroxamic acids. Two new and complementary synthetic pathways were developed. One of them provided macrocyclic hydroxamic acids with size comprising between 24 and 26 atoms

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Wu, Cheng-Hsueh, et 吳政學. « Pharmacokinetics of carbadox and determination of its metabolite ( quinoxaline-2-carboxylic acid ; QCA ) in pigs following a single dose and multiple in-feed dosing ». Thesis, 2008. http://ndltd.ncl.edu.tw/handle/62693073412975175936.

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碩士
國立屏東科技大學
獸醫學系所
96
The tissue distribution and residue depletion of carbadox and its metabolite ( quinoxaline-2-carboxylic acid, QCA ) were investigated in swine after a single oral dose of 3.5 mg/kg body weight of carbadox and multiple dose ( 2 weeks ) in-feed ( 55 ppm ) administration. Plasma, muscle, liver and kidney were sampled pre and post-treatment and subsequently analyzed for carbadox and QCA concentrations using liquid chromatography with tandem mass spectrometry ( LC-MS-MS ). The limits of detection of carbadox and QCA were 0.002 and 0.180 ng/g, the limits of quantitation were 0.005 and 0.606 ng/g for standard solution. Carbadox concentration in plasma was peaked on 2.6 hr after a single oral dose administration, while QCA concentration was still detected in liver ( 1.98 ng/g ) on the fifth week and kidney ( 0.9 ng/g ) on the sixth week after withdrawal. The apparent volume of distribution of carbadox at steady-state ( 4427.39 ± 2070.30 mL/kg ) and areas under the concentration curves ( 2327.58 ± 580.93 hr ng/mL ) indicates that the drug is adequately distributed throughout the body from the blood of pigs. The slow elimination of the carbadox metabolites suggests a need for long withdrawal periods prior to use of dosed swine for human consumption.

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Livres sur le sujet "Carboxylic acids Metabolism"

Winter, Klaus, et J. Andrew C. Smith. Crassulacean Acid Metabolism : Biochemistry, Ecophysiology and Evolution. Springer, 2011.

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Chalmers, R. A. Organic Acids in Man : The Analytical Chemistry, Biochemistry and Diagnosis of the Organic Acidurias. Springer, 2011.

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Beardsley, Grant D. Elimination of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid when normalized to urinary creatinine. 1990.

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Beardsley, Grant D. Elimination of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid when normalized to urinary creatinine. 1990.

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Chapitres de livres sur le sujet "Carboxylic acids Metabolism"

Wermuth, Bendicht. « Inhibition of Aldehyde Reductase by Carboxylic Acids ». Dans Enzymology and Molecular Biology of Carbonyl Metabolism 3, 197–204. Boston, MA : Springer US, 1990. http://dx.doi.org/10.1007/978-1-4684-5901-2_22.

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Rogosa, Morrison, Micah I. Krichevsky et Rita R. Colwell. « Carboxylic Acid or Ester Metabolism ». Dans Springer Series in Microbiology, 174–81. New York, NY : Springer New York, 1986. http://dx.doi.org/10.1007/978-1-4612-4986-3_30.

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Yang, Shang Fa. « Metabolism of 1-Aminocyclopropane-1-Carboxylic Acid in Relation to Ethylene Biosynthesis ». Dans Plant Nitrogen Metabolism, 263–87. Boston, MA : Springer US, 1989. http://dx.doi.org/10.1007/978-1-4613-0835-5_8.

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Honma, M., Y. J. Jia, Y. Kakuta et H. Matsui. « Metabolism of 1-Aminocyclopropane-1-Carboxylic Acid by Penicillium Citrinum ». Dans Biology and Biotechnology of the Plant Hormone Ethylene II, 33–34. Dordrecht : Springer Netherlands, 1999. http://dx.doi.org/10.1007/978-94-011-4453-7_7.

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Pech, Jean-Claude, Mondher Bouzayen, Gilbert Alibert et Alain Latché. « Subcellular Localization of 1-Aminocyclopropane-1-Carboxylic Acid Metabolism in Plant Cells ». Dans Biochemical and Physiological Aspects of Ethylene Production in Lower and Higher Plants, 33–40. Dordrecht : Springer Netherlands, 1989. http://dx.doi.org/10.1007/978-94-009-1271-7_4.

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Sposito, Garrison. « Soil Humus ». Dans The Chemistry of Soils. Oxford University Press, 2016. http://dx.doi.org/10.1093/oso/9780190630881.003.0007.

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Biomoleculesare compounds synthesized to sustain the life cycles of organisms. In soil humus, they are usually products of litter degradation, root excretion, and microbial metabolism, ranging in molecular structure from simple organic acids to complex biopolymers. Organic acids are among the best-characterized biomolecules. Table 3.1 lists five aliphatic (meaning the C atoms are arranged in open-chain structures) organic acids associated commonly with the soil microbiome. These acids contain the unit R—COOH, where COOH is the carboxyl groupand R represents either H or an organic moiety. The carboxyl group can lose its proton easily within the normal range of soil pH (see the third column of Table 3.1) and so is an example of a Brønsted acid. The released proton, in turn, can attack soil minerals to induce their decomposition (see Eq. 1.2), whereas the carboxylate anion (COO-) can form soluble complexes with metal cations, such as Al3+, that are released by mineral weathering [for example, in Eq. 1.7, rewrite oxalate, C2O42-, as (COO-) 2]. The total concentration of organic acids in the soil solution ranges up to 5 mM. These acids tend to have very short lifetimes because of biocycling, but they abide as a component of soil humus, especially its water-soluble fraction, because they are produced continually by microorganisms and plant roots. Formic acid (methanoic acid), the first entry in Table 3.1, is a monocarboxylic acid produced by bacteria and found in the root exudates of maize. Acetic acid (ethanoic acid) also is produced microbially—especially under anaerobic conditions—and is found in root exudates of grasses and herbs. Formic and acetic acid concentrations in the soil solution range from 2 to 5 mM. Oxalic acid (ethanedioic acid), which is ubiquitous in soils, and tartaric acid (D- 2,3-dihydroxybutanedioic acid) are dicarboxylic acids produced by fungi and excreted by plant roots; their soil solution concentrations range from 0.05 to 1 mM. The tricarboxylic citric acid (2-hydroxypropane- 1,2,3-tricarboxylic acid) is also produced by fungi and excreted by plant roots. Its soil solution concentration is less than 0.05 mM.

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Arun, Viswanath, Takashi Mino et Tomonori Matsuo. « METABOLISM OF CARBOXYLIC ACIDS LOCATED IN AND AROUND THE GLYCOLYTIC PATHWAY AND THE TCA CYCLE IN THE BIOLOGICAL PHOSPHORUS REMOVAL PROCESS ». Dans Water Pollution Research and Control Brighton, 363–74. Elsevier, 1988. http://dx.doi.org/10.1016/b978-1-4832-8439-2.50038-9.

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« The Hydrolysis of Carboxylic Acid Esters ». Dans Hydrolysis in Drug and Prodrug Metabolism, 365–418. Zürich : Verlag Helvetica Chimica Acta, 2006. http://dx.doi.org/10.1002/9783906390444.ch7.

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« The Hydrolysis of Carboxylic Acid Ester Prodrugs ». Dans Hydrolysis in Drug and Prodrug Metabolism, 419–534. Zürich : Verlag Helvetica Chimica Acta, 2006. http://dx.doi.org/10.1002/9783906390444.ch8.

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YANG, S. F., Y. LIU, L. SU, G. D. PEISER, N. E. HOFFMAN et T. McKEON. « METABOLISM OF 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID ». Dans Ethylene and Plant Development, 9–21. Elsevier, 1985. http://dx.doi.org/10.1016/b978-0-407-00920-2.50006-8.

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Actes de conférences sur le sujet "Carboxylic acids Metabolism"

Martynenko, Yulia, et Oleksii Antypenko. « Design of Hydrogenated Isoindolylalkyl(Alkaryl-, Aryl-)Carboxylic Acids with Quinazoline Fragment, that Modify the Carbohydrate Metabolism ». Dans International Youth Science Forum “Litteris et Artibus”. Lviv Polytechnic National University, 2018. http://dx.doi.org/10.23939/lea2018.01.155.

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De Clerck, F., R. Van de Wiele, B. Xhonneux, L. Van Gorp, Y. Somers, W. Loots, J. Beetens, J. Van Wauwe, E. Freyne et P. A. J. Janssen. « PLATELET TXA2 SYNTHETASE INHIBITION AND TXA2/PROSTAGLANDIN ENDOPEROXIDE RECEPTOR BLOCKADE COMBINED IN ONE MOLECULE (R 68070) ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643465.

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F 68070, an oxime-alkane carboxylic acid derivative (Janssen Pharmaceutica), is a potent inhibitor of thromboxane A2 (TXA2) synthetase activity (IC50 in vitro against thrombin-stimulated human platelets in plasma : R 68070 : 2.9 x 10-8 M; CGS 13080 : 6 x 10-8 M; OKY-1581 : 8.2 x 10-8 M; dazmegrel : 2.6 x 10-8 M; dazoxiben : 2.3 x 10-8 M).The compound specifically inhibits platelet TXA2 synthetase activity (14C-arachidonic acid metabolism by washed human platelets) without effect on the cyclo-oxygenase, lipoxygenase (platelets, RBL cells) or prostacyclin synthetase activities (rat aortic rings).The inhibitory effect of R 68070 against human platelet TXA2 synthetase activity increases upon prolongation of the contact time (ICsg at 0.5 min of contact : 5.2 x 10-7 M; at 5 min : 8.3 x 10-8 M; at 30 min : 2.5 x 10-8 M) and is reversed by washing of the platelets.In vivo, the compound has a comparatively strong inhibitory effect on platelet TXA2 synthetase activity after oral administration to rats (ED50 - 2 h : R 68070 0.013 mg/kg; CGS-13080 : 0.8 mg/kg; OKY-1581 : 0.61 mg/kg; dazmegrel : 1 mg/kg; dazoxiben : 4.1 mg/kg) and a protracted duration of action in rats and dogs (inhibition 8 h after 1.25 mg/kg orally > 80 %).In vitro, R 68070 inhibits the aggregation of human platelets in plasma stimulated with collagen (IC50 : 4 x 10-6 M), but also with U 46619 (IC50 : 3.8 x 10-6 M) without affecting the primary aggregation reaction elicited by ADP, 5-HT or adrenaline. The compound thus also produces platelet TXA2/prostaglandin endoperoxide receptor blockade.In rats and in dogs R 68070 (1.25 mg/kg I.V.) potently prevents thrombus formation in carotid and coronary arteries damaged by electrical stimulation.The combination of platelet TXA2 synthetase inhibition with TXA2/prostaglandin endoperoxide blockade in one molecule thus might offer an improved anti-thrombotic effectiveness.

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