Showing papers on "Theobromine published in 1984"
TL;DR: The bronchodilator effects and pharmacokinetics of orally administered caffeine and theophylline in a double-blind, single-dose study in asthmatic patients 8 to 18 years of age did not differ significantly and was maximal two hours after ingestion of each drug.
Abstract: We compared the bronchodilator effects and pharmacokinetics of orally administered caffeine (10 mg per kilogram of body weight) and theophylline (5 mg per kilogram) in a double-blind, single-dose study in asthmatic patients 8 to 18 years of age. After 48 hours of withdrawal of all methylxanthines, 13 patients received caffeine and 10 received theophylline. Significant improvements in forced vital capacity, forced expiratory volume in one second, and forced expiratory flow rates occurred from one to six hours after administration of either caffeine or theophylline. The bronchodilator effect of caffeine did not differ significantly from that of theophylline and was maximal two hours after ingestion of each drug. Peak serum levels of caffeine (13.5 +/- 2.9 mg per liter) occurred at one hour, and peak levels of theophylline (8.4 +/- 1.7 mg per liter) at 2.2 +/- 0.8 hours. The mean serum half-time for caffeine was 3.9 +/- 1.4 hours and that for theophylline was 5.8 +/- 1.7 hours. All patients receiving caffeine metabolized it to paraxanthine, theobromine, and theophylline. Mild, transient side effects were seen after both caffeine and theophylline. Vital signs did not change significantly after either drug. We conclude that caffeine, a commonly available chemical, is an effective bronchodilator in young patients with asthma.
75 citations
Book•
01 Jan 1984
TL;DR: The present study focuses on the effects of Caffeine on Monoamine Neurotransmitters in the Central and Peripheral Nervous System, and on the physiological and Behavioral effects of these effects on humans and animals.
Abstract: Section I Metabolism and Kinetics.- I Products of Metabolism of Caffeine.- 1 Discovery and Chemical Structure of Methylxanthines.- 2 Formation of Uric Acid Metabolites.- 3 Introduction of Chromatographic Techniques.- 4 The Metabolic Studies by H.H. Cornish.- 5 Use of Labeled Methylxanthines.- 6 Metabolism of Theophylline in the Premature Infant.- 7 Metabolism of Labeled Theobromine and Identification of Uracil Derivatives.- 8 Use of Methyl-Labeled Caffeine in Breath Tests.- 9 Perinatal Caffeine and Theophylline Metabolism.- 10 Quantitative Metabolic Pathways of Dimethylxanthines.- 11 Identification of an Acetylated Uracil Metabolite in Man.- References.- II Measurement of Caffeine and Its Metabolites in Biological Fluids.- 1 Ultraviolet Spectrophotometry.- 2 Liquid Chromatography.- 3 Thin-Layer Chromatography.- 4 Immunoassays.- 5 Gas Chromatography - Mass Spectrometry.- 6 Carbon Dioxide Breath Test.- 7 Conclusions.- References.- III Interspecies Comparison of Caffeine Disposition.- 1 Absorption.- 2 Plasma Protein Binding.- 3 Distribution.- 4 Clearance.- 4.1 Renal Clearance.- 4.2 Metabolic Clearance.- 4.3 Urinary Metabolism.- 5 Kinetics of Primary Metabolites of Caffeine.- 6 Nonlinear Kinetics.- 7 Chronic Treatment in the Rat.- References.- Section II Intake.- IV Human Consumption of Caffeine.- 1 Introduction.- 2 Sources and Levels.- 2.1 Coffee.- 2.2 Tea.- 2.3 Cocoa and Chocolate Products.- 2.4 Soft Drinks.- 2.5 Drug Products.- 2.6 Standard Caffeine Content Values.- 3 Consumption Data Sources.- 4 Consumption Estimates.- 4.1 Market Research Corporation of America Survey.- 4.2 Market Facts Survey.- 4.3 Nationwide Food Consumption Survey.- 4.4 1982 Coffee Drinking Study.- 4.5 Standard Consumption Estimates.- 4.6 Consumption by Pregnant Women.- 5 Time Distribution of Caffeine Intake.- 6 Summary.- References.- Section III Physiological and Behavioral Effects.- V The Cardiovascular Effects of Caffeine.- 1 Introduction.- 2 Myocardial Contractility.- 3 Heart Rate.- 4 Blood Pressure.- 5 Clinical Pharmacology.- References.- VI Behavioral Effects of Caffeine.- 1 Introduction.- 2 Man.- 2.1 Performance in Laboratory Tests.- 2.2 Individual Variation.- 2.3 Effects in Children.- 2.4 Adverse Effects in Man.- 2.5 Comments on Studies of Behavioral Effects in Human Subjects.- 3 Experimental Animals.- 3.1 Mice.- 3.2 Rats.- 3.3 Other Species.- 4 Conclusions.- References.- Section IV Mechanisms of Effects.- VII Effects of Caffeine on Monoamine Neurotransmitters in the Central and Peripheral Nervous System.- 1 Introduction.- 2 Effects on Brain Monoamines.- 2.1 Serotonin.- 2.2 Catecholamines.- 3 Effects on Catecholamines in the Peripheral Nervous.- System.- References.- VIII Neuroendocrine Effects of Caffeine in Rat and Man.- 1 Introduction.- 2 Studies on Experimental Animals.- 3 Studies in Man.- 4 Conclusions.- References.- IX Adenosine as a Mediator of the Behavioral Effects of Xanthines.- 1 Physiologic Effects of Adenosine.- 2 Adenosine Receptor Localization.- 3 Adenosine Receptor Binding Properties.- 4 Behavioral Effects of Xanthines and Adenosine.- Derivatives.- References.- X Caffeine and the Cardiovascular Effects of Physiological Levels of Adenosine.- 1 Introduction: Caffeine as an Antagonist of Endogenous Adenosine.- 2 Effects of Circulating Adenosine.- 3 Implications of the Interaction of Caffeine with Endogenous Adenosine.- References.- Section V Direct Assessments of Effects on Health Editor of Section V: W. R. Grice.- XI Influence of Ingested Caffeine on Animal Reproduction.- 1 Introduction.- 2 Rats.- 2.1 Details of Experimental Reports.- 2.1.1 Caffeine in Drinking Solution.- 2.1.2 Caffeine in Feed.- 2.2 Summary and Conclusions.- 3 Mice.- 3.1 Details of Experimental Reports.- 3.1.1 Caffeine in Drinking Water.- 3.1.2 Caffeine Administered by Gavage.- 3.1.3 Caffeine Administered by Injection.- 3.2 Summary and Conclusions.- 4 Domestic Chickens.- 5 General Observations.- References.- XII The Teratogenic Potential of Caffeine in Laboratory Animals.- 1 Introduction.- 2 Results of Previous Animal Studies.- 2.1 Concordant Results.- 2.2 Discordant Results.- 3 Previous Reviews of Animal Studies.- 3.1 Federation of American Societies of Biology Report.- 3.2 Citizens' Petition to the Food and Drug Administration..- 3.3 Food and Drug Administration Review of Reproduction and Teratology Studies on Caffeine.- 3.4 National Soft Drink Association's Critique of the Collins Gavage Study.- 3.4.1 Procedural Criticisms.- 3.4.2 Maternal Toxicity.- 3.4.3 Skeletal Variants.- 3.4.4 No-Effect Levels.- 4 Remaining Unresolved Issues.- 4.1 Mechanism(s) of Teratogenic Action in Rodents.- 4.2 Skeletal Variants and Their Biological Significance.- 4.3 Interaction of Caffeine with Known Teratogens.- 4.4 Does Gavage in Animals Induce Complications Secondary to Emotional Stress?.- 5 Summary and Conclusions.- References.- XIII Epidemiologic Studies of Birth Defects.- 1 What Is Epidemiology?.- 2 Why the Need for Epidemiology?.- 3 Limitations of Epidemiology.- 3.1 Associations, Not Causes.- 3.2 Quality of Data.- 3.2.1 Measures of Exposure.- 3.2.2 Outcome Data.- 3.2.3 Covariates.- 3.3 Biases.- 4 The Past.- 5 Recent Publications.- 5.1 Harvard Study.- 5.2 Boston University Study.- 5.3 Loma Linda Study.- 5.4 Yale Study.- 5.5 Overview.- 6 The Future.- References.- XIV The Carcinogenic Potential of Caffeine.- 1 Animal Studies.- 1.1 Published.- 1.2 Unpublished.- 1.3 Cited at Scientific Meetings and in Various Stages of Completion.- 1.4 General Conclusions.- 2 Chemical and Metabolic Studies.- 2.1 Metabolic Evidence.- 2.1.1 Direct Alkylation of DNA or Incorporation into DNA.- 2.1.2 Does Caffeine Undergo Metabolic Activation?.- 2.1.3 Does Caffeine Undergo Covalent Binding?.- 2.2 Structure-Activity Relationships.- 2.3 Associated Biological Activities of Caffeine.- 2.4 Nitrosation Reactions.- 2.5 Summary and Conclusions.- 3 Epidemiological Evidence.- 3.1 Cancer of the Urinary Bladder.- 3.2 Cancer of the Pancreas.- 3.3 Cancer of the Ovary.- 3.4 Conclusions.- 4 Summary of Evidence on Mutagenicity.- References.- XV The Mutagenic Potential of Caffeine.- 1 Introduction.- 2 Exposure.- 3 Results of Mutagenicity Tests.- 3.1 Gene Mutations.- 3.2 Chromosomal Aberrations.- 3.3 Caffeine in Combination with Other Agents.- 3.3.1 Micro-organisms.- 3.3.2 Drosophila melanogaster.- 3.3.3 Plants.- 3.3.4 Mammalian Cells in Culture.- 3.4 Summary and Risk Evaluation for Genetic Effects.- 4 Related Effects of Caffeine.- 4.1 Crossing-over.- 4.2 DNA Repair.- 4.3 Deoxyribonucleotide Pools.- 5 Conclusions.- References.- XVI Mechanism of Potentiation by Caffeine of Genotoxic Damage Induced by Physical and Chemical Agents: Possible Relevance to Carcinogenesis.- 1 Introduction.- 2 Enhancement by Caffeine of Toxicity and Chromosomal Damage Induced by Chemical Agents.- 3 Effects of Caffeine Alone on Normal DNA Replication..- 4 Effects of Genotoxic Agents on DNA Synthesis.- 5 Effects of Post-treatment with Caffeine on DNA Synthesis in Mammalian Cells Treated with Genotoxic Agents.- 6 Caffeine-Induced DNA Template Breakage in Treated Cells: Double-Strand Break Formation.- 7 Caffeine-Induced Premature Mitosis.- 8 Modifying Effects of Caffeine on Tumour Induction by Chemical and Physical Agents: Possible Role of DNA Repair.- 9 Conclusions.- References.
73 citations
TL;DR: In this article, the methylxanthines were identified and quantified with the use of a reverse phase column and theobromine and caffeine levels respectively were 0.695 mg/g and 0.
Abstract: Seventy-nine cocoa or chocolate products and eighteen carob products were analyzed by HPLC for caffeine and theobromine content. After extraction into boiling water, the methylxanthines were identified and quantified with the use of a reverse phase column. Mean theobromine and caffeine levels respectively, were 0.695 mg/g and 0.071 mg/g in cocoa cereals; 1.47 mg/g and 0.152 mg/g in chocolate bakery products; 1.95 mg/g and 0.138 mg/g in chocolate toppings; 2.66 mg/g and 0.208 mg/g in cocoa beverages; 0.621 mg/g and 0.032 mg/g in chocolate ice creams; 0.226 mg/g and 0.011 mg/g in chocolate milks; 74.8 mg/serving and 6.5 mg/serving in chocolate puddings. Theobromine and caffeine levels in carob products ranged from 0-0.504 mg/g and 0-0.067 mg/g, respectively.
71 citations
59 citations
TL;DR: The methylxanthine content of chocolate foods has received only slight attention in the literature, and in children and teenagers, the major dietary source of caffeine was found to be tea, followed by soft drinks and coffee, respectively.
Abstract: This chapter has compiled and evaluated the current information on the methylxanthine composition of cocoa and various chocolate foods and beverages, as well as the consumption pattern for these commodities. Although the earliest recorded reference to cacao was in 1502, it was not until 1876 that milk chocolate was invented, an event that formed the backbone of the chocolate industry today. The consumption of cocoa throughout the world has been influenced by a number of factors, and the period of peak consumption occurred during the early to mid-1960s when these factors were highly favorable. The greatest consumption of cocoa in metric tons over the past 10 yr has been in the United States, although the highest per capita consumer during this period was Switzerland. The African continent has been historically the primary producer of raw cocoa, with the Ivory Coast currently being the largest individual supplier. Limited marketing survey data is available for the consumption of methylxanthines in chocolate foods and beverages. In children and teenagers, the major dietary source of caffeine was found to be tea, followed by soft drinks and coffee, respectively. Although chocolate foods and beverages ranked the lowest of these dietary sources to provide caffeine, they do constitute the major source of dietary theobromine. Cacao is the major natural source of the xanthine base theobromine. Small amounts of caffeine are present in the bean along with trace amounts of theophylline. The methylxanthine content of beans varies with the varietal type, and is influenced by the fermentation process. Chocolate liquor is a semifinished product commonly called "baking" or "cooking" chocolate. The average theobromine and caffeine content of liquors has been reported at 1.2% and 0.21%, respectively. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9% theobromine and 0.21% caffeine. Chocolate beverages comprise the most widely studied category of chocolate products. Hot cocoa provides 62 mg/serving of theobromine and 4 mg/serving of caffeine when prepared from commercial instant mixes. Instant cold chocolate milk mixes supply an average of 58 mg/serving of theobromine and 5 mg/serving of caffeine. The methylxanthine content of chocolate foods has received only slight attention in the literature. The methylxanthine content of sweet chocolate ranges from 0.359 to 0.628% for theobromine and 0.017 to 0.125% for caffeine.(ABSTRACT TRUNCATED AT 400 WORDS)
53 citations
TL;DR: Caffeine appears to be more potent than theobromine as an anorexic agent in rats, but to be equivalent to the Obromine in its potential for inducing thymic atrophy and spermatogenic cell destruction with testicular atrophy.
47 citations
Journal Article•
TL;DR: Caffeine metabolism may be useful as a diagnostic tool to determine an individual's ability to acetylate and thus eliminate potentially harmful compounds from the body, as well as a measure of liver function in terms of enzymatic metabolizing ability.
Abstract: The human disposition of caffeine, theophylline, and theobromine is essentially characterized by rapid and complete gastrointestinal absorption; minimal first pass metabolism; distribution throughout the total body water; extensive and, in the case of caffeine almost complete, biotransformation in the liver; and elimination of metabolites from the body via the kidneys. Methylxanthine metabolism is affected by such factors as diet, smoking, pregnancy, use of oral contraceptives, age, and disease state. These factors have been studied extensively in relationship to caffeine disposition, less so for theophylline, and minimally for theobromine as well as the metabolites of these compounds, in particular paraxanthine and the diaminouracils. The facts that the loss of the 3-methyl group from caffeine to form 1,7-dimethylxanthine (paraxanthine) is the preferential path of metabolism in humans and that an acetylated diaminouracil is one of the major end-products of caffeine metabolism would indicate the need for additional studies of these compounds. The variability often associated with caffeine disposition may be in part genetic in origin since the population is generally biomodally distributed in its ability to acetylate molecules possessing an amino functional group. In addition, caffeine metabolism may be useful as a diagnostic tool to determine an individual's ability to acetylate and thus eliminate potentially harmful compounds from the body, as well as a measure of liver function in terms of enzymatic metabolizing ability.
46 citations
45 citations
TL;DR: It is now clear that theophylline is associated primarily with caffeine biodegradation, whereas theobromine is involved in both biosynthesis and biodegrades of caffeine.
Abstract: The level of theophylline in mature and ripened fruit is 20–50 times that in the immature green fruit of Coffea arabica L. Biodegradation of caffeine occurs in the mature, ripened coffee fruits through theophylline and theobromine as the first biodegradation products. It is now clear that theophylline is associated primarily with caffeine biodegradation, whereas theobromine is involved in both biosynthesis and biodegradation of caffeine.
37 citations
TL;DR: A good correlation was observed between the concentrations of caffeine in serum and in saliva suggesting that salivary measurements may be useful for the study of caffeine pharmacokinetics in man.
Abstract: A method is described for the measurement of theobromine, theophylline and caffeine in serum and saliva by high-performance liquid chromatography (HPLC). A chloroform/isopropanol extract (85:15, v/v) is evaporated to dryness and chromatographed on a 100 X 4.5 mm id Hypersil octadecylsilane column with UV detection at 280 nm. Theobromine, theophylline, caffeine and the internal standard proxyphylline are satisfactorily resolved with an elution system of acetonitrile/tetrahydrofuran/50 mM acetate buffer, pH 4.0, (4:1:95, v/v). No interference is observed from the presence of xanthine metabolites or any of a number of common drugs examined. A good correlation was observed between the concentrations of caffeine in serum and in saliva suggesting that salivary measurements may be useful for the study of caffeine pharmacokinetics in man. Caffeine levels determined by the HPLC procedure described here agreed well with those obtained by a radioimmunoassay method. The method is also suitable for determining the xanthine content of beverages by direct injection of diluted samples.
35 citations
TL;DR: Three male Sprague-Dawley strain rats were trained to respond under a multi-component time out 5 min variable ratio 15 (VR15) schedule of food reinforcement and antagonism of L-PIA was demonstrated from pretreatment with caffeine, theophylline, theobromine, paraxanthine, 3-methylxanthines, and 7- methylxanthine.
Abstract: Three male Sprague-Dawley strain rats were trained to respond under a multi-component time out 5 min variable ratio 15 (VR15) schedule of food reinforcement. Cumulative, within session dose-effect curves were determined for L-PIA alone and after methylxanthine pretreatment. L-PIA alone produced dose related decreases on VR15 responding at doses between 0.032 and 0.178 mg/kg. Significant antagonism of L-PIA was demonstrated from pretreatment with caffeine, theophylline, theobromine, paraxan-thine, 3-methylxanthine, and 7-methylxanthine. No antagonism of L-PIA was observed following pretreatment with 1-methylxanthine. Consistent with the adenosine receptor blockade hypothesis, caffeine also antagonized the effects of 5′-N-ethylcarboxamide adenosine (NECA) on VR15 responding.
Journal Article•
TL;DR: Medulloepithelioma, an embryonal neural tumor, was diagnosed in a 6-month-old Bullmastiff with clinical signs of incomplete, upper motor neuron, transverse myelopathy involving the hindlimbs.
Abstract: Cacao bean shells contain potentially toxic quantities of theobromine, a xanthine compound similar in effects to caffeine and theophylline. A dog, which ingested a lethal quantity of garden mulch made from cacao bean shells, developed severe convulsions and died 17 hours later. Analysis of the stomach contents and the ingested cacao bean shells revealed the presence of lethal amounts of theobromine.
TL;DR: No significant difference was found in the pharmacokinetic profile of the drug after acute or chronic treatment at different doses except for a reduction in the absorption rate constant as the dose increased and AUC values increased in proportion to the dose.
TL;DR: In this article, the thermal behavior of alladium compounds has been studied using TG, DTG and DSC techniques, and enthalpies have been calculated for dehalogenation and dehydration.
TL;DR: In this paper, the complexes AgL (L = theobromine, 1,3,8-trimethylxanthine and 3,8dimethylXanthine) and Hg 2 C 2 (NO 3 ) 2 (C = caffeine) were characterized by IR, 1 H-NMR, TG, DTG and DSC techniques.
TL;DR: Single metabolites showed different degrees of induction at non-saturating concentrations of caffeine and kinetics was non-linear in CO microsomes.
Journal Article•
TL;DR: The results of the dietary surveys showed a fair correlation with plasma caffeine levels, but the surveys are best regarded as a basis for counseling rather than an accurate estimate of intake.
Abstract: Dietary surveys estimated the caffeine intake of pregnant women in London to average 1.4 mmol (270 mg) with a range of 0 to 6.0 mmol (0-1160 mg)/day. The average plasma caffeine was 6.5 (SD 2.8-14.8), plasma theophylline 2.9 (SD 1.3-6.7), plasma theobromine 2.1 (SD 0.9-4.9) mumol/l. The results of the dietary surveys showed a fair correlation (r = 0.59; p less than 0.01) with plasma caffeine levels, but the surveys are best regarded as a basis for counseling rather than an accurate estimate of intake.
TL;DR: Using a number of drugs that increase cellular cAMP levels, alterations in the amount of cell surface fibronectin and other transformation parameters were studied in Chinese hamster ovary (CHO) cells, suggesting that the reverse transformation properties fall into two groups-low saturation density, cell arrest at G1 phase and anchorage-dependent growth.
TL;DR: The well known Hurexide reaction for purine bases was modified and optimized for the quantification of caffeine in crude drugs, refreshing drinks and pharmaceuticals and for the detection and assay of coffee in mixtures of illegal opiate samples.
Abstract: The well known Hurexide reaction for purine bases was modified and optimized for the quantification of caffeine in crude drugs, refreshing drinks and pharmaceuticals. The method was also applied for the detection and assay of caffeine in mixtures of illegal opiate samples. It was also applied to assay theobromine and theophylline alongside with caffeine in their natural and synthretic mixtures after a simple separating procedure depending on their different basicities.
Journal Article•
TL;DR: The presence of theophylline augmented the increase in baseline tension induced by ouabain, although theophyLLine, by itself, did not augment baseline tension at the concentrations tested.
Abstract: The effects of the combined administration of theophylline and ouabain were examined in isolated right ventricular strips from the rabbit heart. Separately, each drug produced positive inotropism. If ouabain was added 10 minutes after theophylline, a decrease in dF/dt was observed. The presence of theophylline augmented the increase in baseline tension induced by ouabain, although theophylline, by itself, did not augment baseline tension at the concentrations tested. There was a significant correlation between the decrease in dF/dt and the rise in baseline tension. Theophylline did not enhance the ability of ouabain to induce arrhythmia. The actions of caffeine, theobromine and digoxin were also examined and gave similar results.
Patent•
29 Nov 1984
TL;DR: In this article, a microorganism in Pseudomonas is allowed to act on caffeine in the presence of nickel ion to effect its conversion into theobromine, and it is shown that it is capable of converting caffeine into a suitable substrate.
Abstract: PURPOSE:A microorganism in Pseudomonas is allowed to act on caffeine in the presence of nickel ion to effect its conversion into theobromine CONSTITUTION:A microorganism in Pseudomonas, capable of converting caffeine into theobromine, eg, Pseudomonas sp188(ERM-7073), or its culture mixture, cell bodies or one of their treated products is allowed to be brought into contact with caffeine in the presence of nickel ion
TL;DR: Evidence is supplied that coacervates can provide a useful model for human cytoplasm by measuring conductivity of xanthines and sugars and finding that caffeine had the highest conductivity, followed by theobromine and theophylline.