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Metabolism of heterocyclic aromatic amines by human hepatocytes and cytochrome P4501A2.
Turesky RJ, Guengerich FP, Guillouzo A, Langouët S
(2002) Mutat Res 506-507: 187-95
MeSH Terms: Animals, Biotransformation, Carcinogens, Cells, Cultured, Chromatography, High Pressure Liquid, Cytochrome P-450 CYP1A2, Dose-Response Relationship, Drug, Hepatocytes, Humans, Imidazoles, Liver, Male, Quinoxalines, Rats, Rats, Sprague-Dawley, Species Specificity, Theophylline
Show Abstract · Added May 26, 2014
The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was investigated in primary human and rat hepatocytes. The genotoxic metabolites 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline (HONH-MeIQx) and 2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), which are formed by cytochrome P4501A2 (CYP1A2), were detected as stable N(2)-glucuronide and N(2)- and N(3)-glucuronide conjugates, respectively. These products accounted for as much as 10% of the amount of MeIQx and 60% of PhIP added to human hepatocytes. Significantly lower amounts of these products were formed in rat hepatocytes. The phase II conjugates N(2)-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl-sulfamic acid (MeIQx-N(2)-SO(3)H) and N(2)-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx-N(2)-Gl), as well as the 7-oxo derivatives of MeIQx and N-desmethyl-MeIQx, 2-amino-3,8-dimethyl-6-hydro-7H-imidazo[4,5-f]quinoxalin-7-one (7-oxo-MeIQx), and 2-amino-6-hydro-8-methyl-7H-imidazo[4,5-f]quinoxalin-7-one (N-desmethyl-7-oxo-MeIQx) were also identified. A novel CYP1A2-derived metabolite was characterized as 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH) and was the predominant metabolite formed in human hepatocytes exposed to MeIQx at levels approaching human exposure. Unlike human hepatocytes, rat cell preparations, even following pretreatment with the potent CYP1A1/CYP1A2 inducer 3-methylcholanthrene (3-MC) did not produce IQx-8-COOH but did catalyze the formation of 2-amino-3,8-dimethyl-5-hydroxyimidazo[4,5-f]quinoxaline (5-HO-MeIQx) as a major CYP-mediated detoxication product. In the case of PhIP, direct glucuronidation of the N(2) and N(3) positions also occurred in human and rat hepatocytes. Glucuronide and sulfate conjugates of 2-amino-4'-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine (4'-HO-PhIP) were detected as relatively minor metabolites in human hepatocytes but were the major products formed in rat hepatocytes, accounting for up to 50% of the metabolism. Rat CYP1A2, but not the human ortholog, significantly contributes to 4'-hydroxylation of PhIP. Important differences exist between human and rat liver enzymes in catalytic activity and regioselectivity of MeIQx and PhIP metabolism. Some human hepatocyte preparations are more active at transforming MeIQx and PhIP to a genotoxic species than rat hepatocytes pretreated with potent inducer 3-MC. These pronounced interspecies differences in metabolism of MeIQx and PhIP may affect the biological activity of these mutagens and must be considered when assessing human health risk.
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17 MeSH Terms
The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes.
Ueng YF, Jan WC, Lin LC, Chen TL, Guengerich FP, Chen CF
(2002) Drug Metab Dispos 30: 349-53
MeSH Terms: Alkaloids, Animals, Chromatography, High Pressure Liquid, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Enzyme System, Enzyme Inhibitors, Humans, In Vitro Techniques, Indole Alkaloids, Kinetics, Magnetic Resonance Spectroscopy, Mice, Mice, Inbred C57BL, Microsomes, Liver, Oxidoreductases, Plant Extracts, Quinazolines, Structure-Activity Relationship, Substrate Specificity, Theophylline
Show Abstract · Added May 26, 2014
Rutaecarpine, evodiamine, and dehydroevodiamine are quinazolinocarboline alkaloids isolated from a traditional Chinese medicine, Evodia rutaecarpa. The in vitro effects of these alkaloids on cytochrome P450 (P450)-catalyzed oxidations were studied using mouse and human liver microsomes. Among these alkaloids, rutaecarpine showed the most potent and selective inhibitory effect on CYP1A-catalyzed 7-methoxyresorufin O-demethylation (MROD) and 7-ethoxyresorufin O-deethylation (EROD) activities in untreated mouse liver microsomes. The IC(50) ratio of EROD to MROD was 6. For MROD activity, rutaecarpine was a noncompetitive inhibitor with a K(i) value of 39 +/- 2 nM. In contrast, rutaecarpine had no effects on benzo[a]pyrene hydroxylation (AHH), aniline hydroxylation, and nifedipine oxidation (NFO) activities. In human liver microsomes, 1 microM rutaecarpine caused 98, 91, and 77% decreases of EROD, MROD, and phenacetin O-deethylation activities, respectively. In contrast, less than 15% inhibition of AHH, tolbutamide hydroxylation, chlorzoxazone hydroxylation, and NFO activities were observed in the presence of 1 microM rutaecarpine. To understand the selectivity of inhibition of CYP1A1 and CYP1A2, inhibitory effects of rutaecarpine were studied using liver microsomes of 3-methylcholanthrene (3-MC)-treated mice and Escherichia coli membrane expressing bicistronic human CYP1A1 and CYP1A2. Similar to the CYP1A2 inhibitor furafylline, rutaecarpine preferentially inhibited MROD more than EROD and had no effect on AHH in 3-MC-treated mouse liver microsomes. For bicistronic human P450s, the IC(50) value of rutaecarpine for EROD activity of CYP1A1 was 15 times higher than the value of CYP1A2. These results indicated that rutaecarpine was a potent inhibitor of CYP1A2 in both mouse and human liver microsomes.
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23 MeSH Terms
Role of adenosine in asthma.
Feoktistov I, Biaggioni I
(1996) Drug Dev Res 39: 333-6
MeSH Terms: Adenosine, Adrenergic beta-Antagonists, Animals, Anti-Asthmatic Agents, Asthma, Bronchoconstriction, Bronchodilator Agents, Dogs, Humans, Lung, Mast Cells, Mice, Rats, Receptors, Adrenergic, alpha-2, Receptors, Adrenergic, beta-2, Theophylline, Xanthines
Show Abstract · Added December 10, 2013
Several lines of evidence support the hypothesis that adenosine contributes to asthma. Inhaled adenosine provokes bronchoconstriction in asthmatics, but not in nonasthmatics. This process appears to be mediated by mast cell activation, because it can be blocked by antihistamines and inhibitors of mast cell activation. Inhaled adenosine evokes release of mast cell mediators in bronchoalveolar lavage fluid, including histamine, prostaglandin D2, and tryptase, a specific mast cell marker. Also, adenosine potentiates the immunological activation of mast cells in vitro, including rat peritoneal mast cells, mouse bone marrow-derived mast cells, human lung mast cells, and the human mast cell line HMC-1. The receptor subtype that mediates this activation differs between mast cell type, but preliminary evidence suggests that human lung mast cells express A2B receptors. An argument against the contribution of adenosine in asthma has been the "enprofylline paradox." This xanthine (3-(n-propylyl)xanthine) is as effective an antiasthmatic as theophylline (1,3-dimethyl xanthine) but was initially thought not to be an adenosine receptor antagonist. More recent evidence has confirmed that enprofylline blocks A2B receptors with a Ki (7 microM) similar to that of theophylline (13 microM) and well within its therapeutic plasma levels (5-25 microM). This finding, we believe, resolves the enprofylline paradox and supports the hypothesis that adenosine, through A2B receptor activation, contributes to asthma. Preliminary evidence suggests that A2B receptors are indeed present in human lung mast cells. A2B receptors, therefore, may be a potential target for the development of antiasthmatic drugs.
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17 MeSH Terms
Regioselective differences in C(8)- and N-oxidation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by human and rat liver microsomes and cytochromes P450 1A2.
Turesky RJ, Parisod V, Huynh-Ba T, Langouët S, Guengerich FP
(2001) Chem Res Toxicol 14: 901-11
MeSH Terms: Amines, Animals, Biotransformation, Cells, Cultured, Cytochrome P-450 CYP1A2, Cytochrome P-450 CYP1A2 Inhibitors, Enzyme Inhibitors, Hepatocytes, Humans, Inactivation, Metabolic, Kinetics, Microsomes, Liver, Mutagens, NADPH-Ferrihemoprotein Reductase, Quinoxalines, Rats, Recombinant Proteins, Species Specificity, Substrate Specificity, Theophylline
Show Abstract · Added May 26, 2014
The metabolism of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was investigated with human and rat liver microsomes, recombinant human cytochrome P450 1A2 (P450 1A2) expressed in Escherichia coli cells, and rat P450 1A2. Human liver microsomes and human P450 1A2 catalyzed the oxidation of the exocyclic amine group of MeIQx to form the genotoxic product 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline (HONH-MeIQx). Human P450 1A2 also catalyzed the oxidation of C(8)-methyl group of MeIQx to form 2-amino-(8-hydroxymethyl)-3-methylimidazo[4,5-f]quinoxaline (8-CH(2)OH-IQx), 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carbaldehyde (IQx-8-CHO), and 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH). Thus, chemically stable C(8)-oxidation products of MeIQx may be useful biomarkers of P450 1A2 activity in humans. Rat liver microsomes were 10-15-fold less active than the human counterpart at both N-oxidation and C(8)-oxidation of MeIQx when expressed as nanomoles of product formed per minute per nanomoles of P450 1A2. Differences in regioselective oxidation of MeIQx were also observed with human and rat liver microsomes and the respective P450 1A2 orthologs. In contrast to human liver microsomes and P450 1A2, rat liver microsomes and purified rat P4501A2 were unable to catalyze the oxidation of MeIQx to the carboxylic derivative IQx-8-COOH, an important detoxication product formed in humans. However, rat liver microsomes and rat P4501A2, but not human liver microsomes or human P450 1A2, extensively catalyzed ring oxidation at the C-5 position of MeIQx to form the detoxication product 2-amino-3,8-dimethyl-5-hydroxyimidazo[4,5-f]quinoxaline (5-HO-MeIQx). There are important differences between human and rat P450 1A2, both in catalytic activities and oxidation pathways of MeIQx, that may affect the biological activity of this carcinogen and must be considered when assessing human health risk.
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20 MeSH Terms
Metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in human hepatocytes: 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid is a major detoxification pathway catalyzed by cytochrome P450 1A2.
Langouët S, Welti DH, Kerriguy N, Fay LB, Huynh-Ba T, Markovic J, Guengerich FP, Guillouzo A, Turesky RJ
(2001) Chem Res Toxicol 14: 211-21
MeSH Terms: Animals, Biotransformation, Cell Separation, Cells, Cultured, Chromatography, High Pressure Liquid, Cytochrome P-450 CYP1A2, Cytochrome P-450 CYP1A2 Inhibitors, Enzyme Inhibitors, Hepatocytes, Humans, In Vitro Techniques, Inactivation, Metabolic, Magnetic Resonance Spectroscopy, Mass Spectrometry, Microsomes, Liver, Mutagens, Quinoxalines, Rats, Theophylline
Show Abstract · Added May 26, 2014
Metabolic pathways of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) remain incompletely characterized in humans. In this study, the metabolism of MeIQx was investigated in primary human hepatocytes. Six metabolites were characterized by UV and mass spectroscopy. Novel metabolites were additionally characterized by 1H NMR spectroscopy. The carcinogenic metabolite, 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline, which is formed by cytochrome P450 1A2 (P450 1A2), was found to be transformed into the N(2)-glucuronide conjugate, N(2)-(beta-1-glucosiduronyl)-2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline. The phase II conjugates N(2)-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl)sulfamic acid and N(2)-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, as well as the 7-oxo derivatives of MeIQx and N-desmethyl-MeIQx, 2-amino-3,8-dimethyl-6-hydro-7H-imidazo[4,5-f]quinoxalin-7-one (7-oxo-MeIQx), and 2-amino-6-hydro-8-methyl-7H-imidazo[4,5-f]quinoxalin-7-one (N-desmethyl-7-oxo-MeIQx), thought to be formed exclusively by the intestinal flora, were also identified. A novel metabolite was characterized as 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH), and it was the predominant metabolite formed in hepatocytes exposed to MeIQx at levels approaching human exposure. IQx-8-COOH formation is catalyzed by P450 1A2. This metabolite is a detoxication product and does not induce umuC gene expression in Salmonella typhimurium strain NM2009. IQx-8-COOH is also the principal oxidation product of MeIQx excreted in human urine [Turesky, R., et al. (1998) Chem. Res. Toxicol. 11, 217-225]. Thus, P450 1A2 is involved in both the metabolic activation and detoxication of this procarcinogen in humans. Analogous metabolism experiments were conducted with hepatocytes of untreated rats and rats pretreated with the P450 inducer 3-methylcholanthrene. Unlike human hepatocytes, the rat cell preparations did not produce IQx-8-COOH but catalyzed the formation of 2-amino-3,8-dimethyl-5-hydroxyimidazo[4,5-f]quinoxaline as a major P450-mediated detoxication product. In conclusion, our results provide evidence of a novel MeIQx metabolism pathway in humans through P450 1A2-mediated C(8)-oxidation of MeIQx to form IQx-8-COOH. This biotransformation pathway has not been detected in experimental animal species. Considerable interspecies differences exist in the metabolism of MeIQx by P450s, which may affect the biological activity of this mutagen and must be considered when assessing human health risk.
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19 MeSH Terms
Underutilization of controller and rescue medications among older adults with asthma requiring hospital care.
Hartert TV, Togias A, Mellen BG, Mitchel EF, Snowden MS, Griffin MR
(2000) J Am Geriatr Soc 48: 651-7
MeSH Terms: Administration, Inhalation, Administration, Oral, Administration, Topical, Adrenergic beta-Agonists, Aged, Aged, 80 and over, Analysis of Variance, Anti-Asthmatic Agents, Anti-Bacterial Agents, Anti-Inflammatory Agents, Asthma, Bronchodilator Agents, Chronic Disease, Drug Utilization Review, Female, Glucocorticoids, Guideline Adherence, Health Resources, Humans, Male, Medicaid, Retrospective Studies, Severity of Illness Index, Tennessee, Theophylline, United States
Show Abstract · Added May 27, 2014
BACKGROUND - Asthma causes serious morbidity in older people, but pharmacologic therapy in older people with asthma has never been studied, at least in part because of the difficulty of defining asthma in this population.
OBJECTIVE - To determine if older persons enrolled in Medicaid and hospitalized with an exacerbation of asthma receive appropriate outpatient asthma care.
DESIGN - Descriptive pharmacoepidemiology of a group of older adults with asthma.
SETTING - The Tennessee Medicaid Program.
PARTICIPANTS - Persons aged 65 and older, enrolled in the Tennessee Medicaid program, identified through Medicaid's computerized database as having a hospital care visit for asthma in 1992 and who had their diagnosis confirmed by chart review.
MEASUREMENT - Medication utilization.
RESULTS - The source population included 93,686 persons aged 65 or older enrolled in the Tennessee Medicaid program. The group meeting study criteria included 512 patients with chronic asthma who had a hospital care visit for an asthma exacerbation. Eighty-one percent of these 512 persons with an asthma hospitalization confirmed by chart review were classified as having moderate to severe or potentially fatal asthma. These patients had had a median of 15 outpatient visits in the previous year, and more than half of them had an outpatient visit in the 14 days before their hospitalization. However, among those with moderate to severe or near fatal asthma only 25% filled prescriptions for inhaled corticosteroids, whereas 52% were taking theophylline, the most commonly prescribed asthma medication in this group. There was also high use of antibiotics (29%) and low use of rescue corticosteroids (5%) before the hospital care visit, despite frequent medical encounters.
CONCLUSIONS - Despite widespread promulgation of the National Asthma Education Prevention Program guidelines, our study suggests that providers caring for indigent older subjects with moderate to severe or potentially fatal asthma were not following these guidelines. There was significant underutilization of inhaled anti-inflammatory agents, beta-agonists, and rescue corticosteroids in this population despite frequent outpatient medical care visits.
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26 MeSH Terms
Superoxide radical scavenging by phenolic bronchodilators under aprotic and aqueous conditions.
Zwicker K, Damerau W, Dikalov S, Scholtyssek H, Schimke I, Zimmer G
(1998) Biochem Pharmacol 56: 301-5
MeSH Terms: Adrenergic beta-Agonists, Albuterol, Bronchodilator Agents, Drug Combinations, Electron Spin Resonance Spectroscopy, Fenoterol, Free Radical Scavengers, Metaproterenol, Superoxides, Theophylline
Show Abstract · Added March 26, 2019
Asthmatic airway disease is accompanied by the appearance of inflammatory cells which produce reactive oxygen species (ROS). Therefore, the radical scavenging properties of the bronchodilators reproterol, fenoterol, salbutamol and terbutaline toward superoxide anion radicals and hydroperoxyl radicals were investigated in a model system by electron paramagnetic resonance spectroscopy (EPR) and photometric approaches. The substances under study showed activity in superoxide radical scavenging under aprotic and protic conditions as well. The efficiency of the reaction decreased in the order: fenoterol > salbutamol > reproterol > terbutaline > oxyfedrine when DMSO was used as an aprotic solvent. In an aqueous system, the rate constants decreased in the order: fenoterol > reproterol > salbutamol. It is suggested that the antioxidant effect of these beta2-agonists is an additional advantage in treatment of asthmatic lung disease, reducing the negative consequences of airway inflammation.
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Reconstitution of recombinant cytochrome P450 2C10(2C9) and comparison with cytochrome P450 3A4 and other forms: effects of cytochrome P450-P450 and cytochrome P450-b5 interactions.
Yamazaki H, Gillam EM, Dong MS, Johnson WW, Guengerich FP, Shimada T
(1997) Arch Biochem Biophys 342: 329-37
MeSH Terms: Animals, Aryl Hydrocarbon Hydroxylases, Chlorzoxazone, Cytochrome P-450 CYP2C9, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System, Cytochromes b5, Escherichia coli, Ethanolamines, Humans, Hydroxylation, Mixed Function Oxygenases, Mutation, NADP, Nifedipine, Oxidation-Reduction, Phospholipids, Recombinant Proteins, Testosterone, Theophylline, Tolbutamide, Warfarin
Show Abstract · Added May 26, 2014
Tolbutamide methyl hydroxylation and S-warfarin 7-hydroxylation activities were reconstituted in systems containing recombinant human cytochrome P450 (P450 or CYP) 2C10(2C9) and the optimal conditions for the systems were compared with those of bufuralol 1'-hydroxylation by CYP1A1, theophylline 8-hydroxylation by CYP1A2, bufuralol 1'-hydroxylation by CYP2D6, chlorzoxazone 6-hydroxylation by CYP2E1, and testosterone 6 beta-hydroxylation by CYP3A4. CYP2C10 required cytochrome b5 (b5) for optimal rates of tolbutamide and S-warfarin oxidations and b5 could be replaced by apo-b5; apo-b5 and b5 effects on the reconstituted systems have already been reported in systems containing CYP3A4 for the oxidation of testosterone and nifedipine and for the rapid reduction of CYP3A4 by NADPH-P450 reductase (H. Yamazaki et al., 1996, J. Biol. Chem. 271, 27438-27444). Stopped-flow studies, however, suggested that apo-b5 as well as b5 did not cause stimulation of the reduction of CYP2C10 by NADPH-P450 reductase, while the reduction rates were dependent on the substrates in reconstituted systems. Chlorzoxazone 6-hydroxylation by CYP2E1 was stimulated by b5, but not by apo-b5, in reconstituted systems. Neither apo- nor holo-b5 increased bufuralol 1'-hydroxylation activity by CYP1A1 or 2D6 or theophylline 8-hydroxylation by CYP1A2. Interestingly, we found that testosterone 6 beta-hydroxylation by CYP3A4 was stimulated by CYP1A2 (and also by a modified form in which the first 36 residues of the native human protein were removed) and CYP1A1 as well as by b5, and such stimulations were not seen when other P450 proteins (e.g., CYP2C10, 2D6, or 2E1) were added to the reconstituted systems. In contrast, substrate oxidations by CYP2C10 and CYP2E1 were not stimulated by other P450 proteins. The present results suggest that there are differences in optimal conditions for reconstitution of substrate oxidations by various forms of human P450 enzymes, and in some P450-catalyzed reactions protein-protein interactions between P450 and b5 and other P450 proteins are very important in some oxidations catalyzed by CYP2C10, 2E1, and 3A4.
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22 MeSH Terms
Role of adenosine in the sympathetic activation produced by isometric exercise in humans.
Costa F, Biaggioni I
(1994) J Clin Invest 93: 1654-60
MeSH Terms: Adenosine, Adult, Blood Pressure, Dose-Response Relationship, Drug, Exercise, Female, Humans, Male, Muscles, Reflex, Sympathetic Nervous System, Theophylline
Show Abstract · Added December 10, 2013
Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96 +/- 25% (n = 6, P < 0.01) and MABP by 12 +/- 3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 microgram/ml forearm per min) blocked the increase in MSNA (92 +/- 15% vs. 28 +/- 6%, n = 7, P < 0.01) and MABP (38 +/- 6 vs. 27 +/- 4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans.
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12 MeSH Terms
Dose conversion from aminophylline to theophylline in preterm infants.
Reese J, Prentice G, Yu VY
(1994) Arch Dis Child Fetal Neonatal Ed 71: F51-2
MeSH Terms: Administration, Oral, Aminophylline, Biological Availability, Humans, Infant, Infant, Newborn, Infusions, Intravenous, Infusions, Parenteral, Prospective Studies, Theophylline
Show Abstract · Added May 26, 2015
Twenty two preterm infants were prospectively evaluated to assess the need for dose adjustment when converting enteral and parenteral routes of methylxanthine administration.Serum theophylline concentrations remained unchanged in 18 infants after conversion from intravenous aminophylline to theophylline by mouth without dose reduction, as is currently recommended [corrected]. Intravenous aminophylline and theophylline by mouth may therefore be prescribed at equivalent doses, with a possible reduction in drug errors, and improved stability of serum concentrations.
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10 MeSH Terms