Sample records for 1,3,7-trimethylxanthine

  1. GIAO NMR calculations of some novel 8-thio-substituted 1,3,7-trimethylxanthines: comparison of theoretical and experimental H-1 chemical shifts

    Stanchev, Stancho; Mitkov, J.; Georgieva, M.; Zlatkov, A.


    Roč. 26, č. 6 (2012), s. 3424-3433. ISSN 1310-2818 Institutional research plan: CEZ:AV0Z40550506 Keywords : H-1 NMR * DFT * GIAO * 8-thiosubstituted 1,3,7-trimethylxanthines Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.622, year: 2012

  2. DFT study of the physicochemical characteristics and spectral behavior of new 8-substituted 1,3,7-trimethylxanthines

    Stanchev, Stancho; Mitkov, J.; Georgieva, M.; Zlatkov, A.


    Roč. 113, č. 9 (2013), s. 1384-1393. ISSN 0020-7608 Institutional support: RVO:61388963 Keywords : caffeine derivates * quantum chemical properties * spectral properties * DFT methods Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.166, year: 2013

  3. Caffeine Enhances the Calcium-Dependent Cardiac Mitochondrial Permeability Transition: Relevance for Caffeine Toxicity

    Sardão, Vilma A; Oliveira, Paulo J; Moreno, António J. M.


    Caffeine (1,3,7-trimethylxanthine), a compound present in beverages such as tea and coffee, is known to be toxic at high concentrations. Some of the observed clinical conditions include cardiovascular disease and reproductive disorders, among others. The possible toxic effects of caffeine on heart mitochondria are still poorly understood. The influence of caffeine on the mitochondrial permeability transition has not been clarified so far. The objective of this study was to investigate whether...

  4. Potential of [11C]TMSX for the evaluation of adenosine A2A receptors in the skeletal muscle by positron emission tomography

    We examined the potential of [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) for the assessment of adenosine A2A receptors in muscle. In rodents, specific binding of [11C]TMSX was observed in muscle and heart by blockade with A2A-selective CSC and non-selective theophylline, but not with A1-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [11C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding

  5. Potential of [{sup 11}C]TMSX for the evaluation of adenosine A{sub 2A} receptors in the skeletal muscle by positron emission tomography

    Ishiwata, Kiichi E-mail:; Mizuno, Masaki; Kimura, Yuichi; Kawamura, Kazunori; Oda, Keiichi; Sasaki, Toru; Nakamura, Yoshio; Muraoka, Isao; Ishii, Kenji


    We examined the potential of [7-methyl-{sup 11}C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([{sup 11}C]TMSX) for the assessment of adenosine A{sub 2A} receptors in muscle. In rodents, specific binding of [{sup 11}C]TMSX was observed in muscle and heart by blockade with A{sub 2A}-selective CSC and non-selective theophylline, but not with A{sub 1}-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [{sup 11}C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding.


    Neha Rani


    Full Text Available Toxic ingredients of Pharmaceutical as well as Food grade food supplements / Dietary Supplement are Pygeum, Caffeine / Caffeine extract, Omega 3 fatty acid (source fish oil, flaxseed oil, or cod liver oil, Ephedrine (Ephedra sinica , Usnic acid, Kava-Kava (Piper methysticum, Gugulipid (Comiphora mukul, Liquorice (Glycyrrhiza glabra,  Ginseng  (Panax ginseng, Panax japonicus, Panax trifolius, Panax zingiberensis, Panax bipinnatifidus, St. John's wort (Hypericum perforatum etc. Caffeine (1,3,7-trimethylxanthine is an alkaloid of the methylxanthine family known as a central nervous system stimulant through its adenosine antagonist action. Caffeine is a naturally found in the leaves, seeds and/or fruits of at least 63 plant species worldwide. Caffeine produces psychoactive responses (alertness, mood change, neurological condition (infant hyperactivity, Parkinson’s disease, metabolic disorders (diabetes, gallstones, and gonad and liver function. However, high doses may produce negative effects in some sensitive individuals, including anxiety, tachycardia and insomnia recommended upper limits of caffeine for healthy adults below 300-500 mg daily, pregnant women must stay below 150-200 mg daily and children should stay below 50 mg daily. Amounts exceeding 700 milligrams of caffeine can be dangerous. Key words: Caffeine, CNS stimulant

  7. Caffeine protects mice against whole-body lethal dose of γ-irradiation

    Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of γ-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

  8. Mutant quantity and quality in mammalian cells (AL) exposed to cesium-137 gamma radiation: Effect of caffeine

    We examined the effect of caffeine (1,3,7-trimethylxanthine) on the quantity and quality of mutations in cultured mammalian AL human-hamster hybrid cells exposed to 137Cs γ radiation. At a dose (1.5 mg/ml for 16 h) that reduced the plating efficiency (PE) by 20%, caffeine was not itself a significant mutagen, but it increased by approximately twofold the slope of the dose-response curve for induction of S1- mutants by 137Cs γ radiation. Molecular analysis of 235 S1- mutants using a series of DNA probes mapped to the human chromosome 11 in the AL hybrid cells revealed that 73 to 85% of the mutations in unexposed cells and in cells treated with caffeine alone, 137Cs γ rays alone or 137Cs γ rays plus caffeine were large deletions involving millions of base pairs of DNA. Most of these deletions were contiguous with the region of the MIC1 gene at 11p13 that encodes the S1 cell surface antigen. In other mutants that had suffered multiple marker loss, the deletions were intermittent along chromosome 11. These open-quotes complexclose quotes mutations were rare for 137Cs γ irradiation (1/63 = 1.5%) but relatively prevalent (23-50%) for other exposure conditions. Thus caffeine appears to alter both the quantity and quality of mutations induced by 137Cs γ irradiation. 62 refs., 3 figs., 3 tabs

  9. Greater adenosine A2A receptor densities in cardiac and skeletal muscle in endurance-trained men: a [11C]TMSX PET study

    We examined the densities of adenosine A2A receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A2A receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A2A receptors was evaluated as the distribution volume of [11C]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [11C]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [11C]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6±0.3 vs. 3.1±0.4 ml g-1; triceps brachii muscle, 1.7±0.3 vs. 1.2±0.2 ml g-1, respectively). These results indicate that the densities of adenosine A2A receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men

  10. Preclinical studies on [11C]TMSX for mapping adenosine A2A receptors by positron emission tomography

    In previous in vivo studies with mice, rats and monkeys, we have demonstrated that [11C]TMSX ([7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)- 1,3,7-trimethylxanthine) is a potential radioligand for mapping adenosine A2A receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. A suitable preparation method for [11C]TMSX injection was established. The radiation absorbed-dose by [11C]TMSX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of TMSX were not found. The striatal uptake of [11C]TMSX in mice was reduced by pretreatment with theophylline at the dose of 10 and 100 mg/kg, suggesting that the [11C]TMSX PET should be carefully performed in the patients received with theophylline. We have concluded that [11C]TMSX is suitable for mapping adenosine A2A receptors in the human brain by PET. (author)

  11. Production of Recombinant Caffeine Synthase from Guarana (Paullinia cupana var. sorbilis) in Escherichia coli.

    Schimpl, Flávia Camila; Kiyota, Eduardo; Mazzafera, Paulo


    Caffeine synthase (CS) is a methyltransferase responsible for the last two steps of the caffeine biosynthesis pathway in plants. CS is able to convert 7-methylxanthine to theobromine (3,7-dimethylxanthine) and theobromine to caffeine (1,3,7-trimethylxanthine) using S-adenosyl-L-methionine as the methyl donor in both reactions. The production of a recombinant protein is an important tool for the characterization of enzymes, particularly when the enzyme has affinity for different substrates. Guarana has the highest caffeine content among more than a hundred plant species that contain this alkaloid. Different from other plants, in which CS has a higher affinity for paraxanthine (1,7-dimethylxanthine), caffeine synthase from guarana (PcCS) has a higher affinity for theobromine. Here, we describe a method to produce a recombinant caffeine synthase from guarana in Escherichia coli and its purification by affinity chromatography. The recombinant protein retains activity and can be used in enzymatic assays and other biochemical characterization studies. PMID:26843165

  12. Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster.

    Alexandra Coelho

    Full Text Available Caffeine (1, 3, 7-trimethylxanthine, an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents. A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs that were highly overexpressed. Flies treated with metyrapone--an inhibitor of CYP enzymes--showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects.

  13. Potential of an adenosine A2A receptor antagonist [11C]TMSX for myocardial imaging by positron emission tomography. A first human study

    In previous in vivo studies with mice, rats, cats and monkeys, we have demonstrated that [7-methyl-11C]-(E)-8-(3,4,5-trimethoxy styryl)-1,3,7-trimethylxanthine ([11C]TMSX) is a potential radioligand for mapping adenosine A2A receptors of the brain by positron emission tomography (PET). In the present study, we studied the potential of [11C]TMSX for myocardial imaging. Uptake of radioactivity by the heart was high and gradually decreased after an intravenous injection of [11C]TMSX into mice. In metabolite analysis, 54% and 76% of the radioactivity in plasma and heart, respectively, were present as the unchanged form of [11C]TMSX 60 min postinjection. The myocardial uptake was reduced by carrier-loading and by co-injection of an adenosine A2A antagonist CSC, but not by co-injection of an adenosine A1 antagonist DPCPX. Pretreatment with a high dose of a non-selective antagonist theophylline also reduced the myocardial uptake of [11C]TMSX. These findings demonstrate the specific binding of [11C]TMSX to adenosine A2A receptors in the heart. Finally we successfully performed the myocardial imaging by PET with [11C]TMSX in a normal volunteer. A graphical analysis by Logan plot supported the receptor-mediated uptake of [11C]TMSX. Peripherally [11C]TMSX was very stable in human: >90% of the radioactivity in plasma was detected as the unchanged form in a 60-min study. We concluded that [11C]TMSX PET has the potential for myocardial imaging. (author)

  14. Caffeine synthase and related methyltransferases in plants.

    Misako, Kato; Kouichi, Mizuno


    Caffeine (1,3,7-trimethylxanthine) is a purine alkaloid present in high concentrations in tea and coffee and it is also found in a number of beverages such as coca cola. It is necessary to elucidate the caffeine biosynthetic pathway and to clone the genes related to the production of caffeine not only to determine the metabolism of the purine alkaloid but also to control the content of caffeine in tea and coffee. The available data support the operation of a xanthosine-->7-methylxanthosine-->7-methylxanthine-->theobromine-->caffeine pathway as the major route to caffeine. Since the caffeine biosynthetic pathway contains three S-adenosyl-L-methionine (SAM) dependent methylation steps, N-methyltransferases play important roles. This review focuses on the enzymes and genes involved in the methylation of purine ring. Caffeine synthase, the SAM-dependent methyltransferase involved in the last two steps of caffeine biosynthesis, was originally purified from young tea leaves (Camellia sinensis). The isolated cDNA, termed TCS1, consists of 1,483 base pairs and encodes a protein of 369 amino acids. Subsequently, the homologous genes that encode caffeine biosynthetic enzymes from coffee (Coffea arabica) were isolated. The recombinant proteins are classified into the three types on the basis of their substrate specificity i.e. 7-methylxanthosine synthase, theobromine synthase and caffeine synthase. The predicted amino acid sequences of caffeine biosynthetic enzymes derived from C. arabica exhibit more than 80% homology with those of the clones and but show only 40% homology with TCS1 derived from C. sinensis. In addition, they share 40% homology with the amino acid sequences of salicylic carboxyl methyltransferase, benzoic acid carboxyl methyltransferase and jasmonic acid carboxyl methyltransferase which belong to a family of motif B' methyltransferases which are novel plant methyltransferases with motif B' instead of motif B as the conserved region. PMID:14977590

  15. Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit.

    Schimpl, Flávia Camila; Kiyota, Eduardo; Mayer, Juliana Lischka Sampaio; Gonçalves, José Francisco de Carvalho; da Silva, José Ferreira; Mazzafera, Paulo


    Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein. PMID:24856135

  16. Adenosine A(2A receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

    Masahiro Mishina

    Full Text Available Adenosine A(2A receptors (A2ARs are thought to interact negatively with the dopamine D(2 receptor (D2R, so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD. However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET with [7-methyl-(11C]-(E-8-(3,4,5-trimethoxystyryl-1,3,7-trimethylxanthine ([(11C]TMSX in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test. In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test. In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an

  17. Consumo de cafeína e prematuridade Caffeine intake and prematurity

    Rita Adriana Gomes de Souza


    Full Text Available A cafeína (1, 3, 7-trimetilxantina é uma metilxantina que facilmente atravessa a barreira placentária, com quantidades substanciais passando para o líquido amniótico, sangue do cordão umbilical, plasma e urina dos neonatos. As maiores fontes de cafeína são café, chá, chocolate e refrigerantes do tipo cola. Além disso, cerca de mil drogas prescritas e 2 mil drogas não prescritas contêm cafeína, e 25 dessas drogas podem ser usadas na gravidez. Embora estudos em animais indiquem que a cafeína leve à diminuição no crescimento intrauterino fetal, redução do peso ao nascer, reabsorção fetal e teratogênese, nos estudos epidemiológicos os achados são, ainda, inconclusivos. Pelo fato de os alimentos com cafeína serem amplamente consumidos na gravidez, é importante avaliar se o uso dessa substância está associado com a redução da idade gestacional. Este artigo examina o conhecimento atual do consumo de cafeína durante a gravidez, abordando os estudos epidemiológicos sobre a associação entre consumo de cafeína e prematuridade, as fontes de cafeína e seu consumo na gravidez, a bioquímica, a fisiopatologia e a plausibilidade biológica da associação e as principais limitações dos estudos sobre cafeína e prematuridade.Caffeine (1, 3, 7-trimethylxanthine is a methylxanthine that easily crosses the placental barrier, substantial amounts passing into the amniotic fluid, umbilical cord blood, and the plasma and urine of the neonates. The main sources of caffeine are coffee, tea, chocolate and cola soft drinks. Moreover, about 1000 prescribed drugs and 2000 non-prescribed drugs contain caffeine, and 25 of these drugs can be used during pregnancy. Although animal studies indicate that caffeine leads to a decrease in fetal intrauterine growth, low birth weight, fetal re-absorption and teratogenesis, these findings are still inconclusive in the epidemiological studies. Since foods containing caffeine are widely consumed