Showing papers on "Theobromine published in 1997"

Recent advances in caffeine and theobromine toxicities: a review

Abstract: Caffeine and theobromine are purine alkaloids widely consumed as stimulants and snacks in coffee and cocoa based foods and most often as part of ingredients in drugs. Man has enjoyed a long history of consumption of caffeine and theobromine. Recent interest in these two alkoloids, however, is centered on their potential reproductive toxicities. Caffeine and theobromine are now known to cross the placental and blood brain barrier thus potentially inducing fetal malformation by affecting the expression of genes vital in development. The developing fetus may not have developed enzymes for detoxification of these methylxanthine alkaloids via demethylation. There is a need, therefore, to protect the conceptus against ‘insults’ from teratogens of this nature. Apart from its reproductive toxicity, the presence of caffeine and theobromine in cocoa could limit its potentials as a nourishing food. This is an issue that needs to be addressed by nutritionists and the food industry at large. This paper discusses the natural sources, consumption and uses, toxicity and the major advances in the reproductive toxicology of caffeine and theobromine. The biosynthesis of these compounds in plants, metabolism in mammalian systems and the involvement of cytochrome P450 are reviewed and summarized. Evidence in favor of the toxicity of these compounds in experimental animals is presented with emphasis on the implications of these findings in humans. The paper concludes with a call for caution in the use of caffeine and theobromine pending further and more elaborate investigations.

Evaluation of xanthine derivatives in chocolate – nutritional and chemical aspects

Abstract: Organic substances containing nitrogen are widespread throughout the whole of the natural world. Also included amongst these are the methylxanthine derivatives caffeine, theobromine and theophylline. These are very closely related and are to be found in extremely varying contents in different plants. Because of their pharmacological effect, which is fundamentally of a stimulative nature, methylxanthines have been significant since time immemorial as luxury, non-essential foodstuffs and as medication. These substances are often referred to as alkaloids. Theobromine is the major alkaloid in cacao (Theobroma cacao). Caffeine, on the other hand, is only to be found in cacao in very small quantities and theophylline only in trace amounts. Methylxanthines are said to contribute towards the typically bitter taste of cacao. In addition they represent important analytical parameters with regard to the evaluation of the quality of cacao-containing and chocolate products. The amount of methylxanthines in cacao depends on various influencing factors, the most essential ones being processing procedures, genotype, geographical origin and cacao bean weight. By determining the amount of theobromine and caffeine in cacao and/or cacao products, the amount of fat-free dry cacao can also be estimated. There are various methods available for the detection and determination of methylxanthines. UV-spectrophotometric determination and analysis using HPLC have attained major significance here. With regard to human nutrition, cacao and cacao products are the main natural sources of theobromine, but significantly less so with regard to caffeine. The presence of methylxanthines in cacao products leads to that they are sometimes the subject of consumer criticism, particularly because they are considered as luxury foodstuffs. The concluding evaluation of methylxanthines by dieticians and toxicologists reveals that plants that contain methylxanthines have been consumed for as long as can be remembered without having led to damage to health. Scientific research has shown that the consumption of these substances has no consequence whatsoever, as long as consumption is not excessive, which is the case for all foodstuffs. Methylxanthines in cacao products have no negative effects on the health of humans because their amounts in chocolates and other processed foodstuffs containing cacao are so low that they account for only a very small proportion of the whole of the human diet.

Metabolism of Caffeine and Related Purine Alkaloids in Leaves of Tea (Camellia sinensis L.)

Abstract: Purine alkaloid catabolism pathways in young, mature and aged leaves of tea (Camellia sinensis L.) were investigated by incubating leaf sections with l4 C-labelled theobromine, caffeine, theophylline and xanthine. Incorporation of label into CO2 was determined and methanolsoluble metabolites were analysed by high-performance liquid chromatography-radiocounting and thin layer chromatography. The data obtained demonstrate that theobromine is the immediate precursor of caffeine, which accumulates in tea leaves because its conversion to theophylline is the rate limiting step in the purine alkaloid catabolism pathway. The main fate of [8- 14 C]theophylline incubated with mature and aged leaves, and to a lesser extent young leaves, is conversion to 3-methylxanthine and onto xanthine which is degraded to 14 CO2 via the purine catabolism pathway. However, with young leaves, sizable amounts of [8- 14 C]theophylline were salvaged for the synthesis of caffeine via a 3-methylxanthine —»• theobromine —* caffeine pathway. Trace amounts of [2- 14 C]xanthine were also salvaged for caffeine biosynthesis in young leaves, by conversion to 3methylxanthine, and this was enhanced in the presence of 5 mM allopurinol which inhibits purine catabolism. Feeds of [2- 14 C]xanthine to young leaves also indicated that 3

Convulsant effects of some xanthine derivatives in genetically epilepsy-prone rats.

Abstract: The behavioural and electrocorticographic (ECoG) convulsant effects of several xanthine derivatives injected intraperitoneally (i.p.) were studied in genetically-epilepsy prone rats. The aim of the study was to evaluate the relationship among convulsant potency, molecular structure and lipophilicity of some xanthines. Animals were injected i.p. with various doses (250-1000 mmol/kg) and a different convulsant potency was observed among the various xanthines tested. IBMX (3-isobutyl-1-methylxanthine), theophylline (1,3-dimethylxanthine) and caffeine (1,3,7-trimethylxanthine) induced an epileptogenic pattern that consisted in an initial phase characterized by wet-dog shakes followed by head tremor, nodding, clonic convulsion and they appeared to be the most potent xanthines among those studied. During seizures, the electrocortical activity was usually characterized by single or multiple sharp- or spike-wave episodes followed by polyspike discharges. After the highest doses of IBMX, theophylline and caffeine, the animals react with falling down, transient tonic clonic seizures, escape response and generalized seizures followed by post-ictal period. Equimolar doses of 8-chlorotheophylline and theobromine (3,7-dimethylxanthine) produced less evident epileptic responses in comparison to previous compounds, whereas no epileptic signs were observed following the administration of enprofylline (3-propylxanthine), etofylline [7-(2-hydroxyethyl)theo-phylline], diprophylline [7-(2,3-dihydroxy-propyl)theo-phylline] and doxofylline [7-(1,3-dioxolan-2-ylmethyl) theophylline]. Lipophylicity of the compounds was determined, but no convincing correlations were found between the rank order of lipophilicities and the convulsant potencies of the compounds studied. On the other hand, structure-activity relationship was also investigated. We suggest that the substitution pattern on the xanthine nucleus may explain, in part, the different convulsant potency of the compounds studied. Furthermore, a selective antagonism of adenosine subtype receptors should be considered.

Comparative pharmacokinetics of caffeine and three metabolites in clinically normal horses and donkeys.

Abstract: OBJECTIVE: To determine whether clearance of capacity-limited drugs in horses differs from that in donkeys by comparing the serum disposition of caffeine and its metabolites, theophylline, theobromine, and paraxanthine after i.v. administration of caffeine to horses and donkeys. ANIMALS: 4 healthy horses and 5 healthy donkeys. PROCEDURE: Blood samples were collected from each animal at time 0 (before) and 5, 10, 15, 20, 30, and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24, 30, 36, 48, 54, 60, 72, and 96 hours after IV administration of a bolus of caffeine. Serum was analyzed in triplicate by high-performance liquid chromatography to determine caffeine, theophylline, theobromine, and paraxanthine concentrations. The serum concentration-time curves for each animal were analyzed separately to estimate model-independent pharmacokinetic variables. RESULTS: Mean pharmacokinetic values for caffeine, theophylline, and paraxanthine did not differ significantly in horses, compared with donkeys. Mean peak serum concentration of theobromine was significantly higher in donkeys, compared with horses. CONCLUSION: Clearance of the capacity-limited drug caffeine does not appear to differ in horses, compared with donkeys. CLINICAL RELEVANCE: For some drugs that undergo hepatic metabolism, the dose and dose interval used for horses may be appropriate for use in donkeys.

Chocolate poisoning in dogs.

Abstract: Yes, chocolate is toxic to dogs (and cats!). While rarely fatal, chocolate ingestion can result in significant illness. Chocolate is toxic because it contains a chemical called theobromine, as well as caffeine. Theobromine is the predominant toxin in chocolate and is very similar to caffeine. Both chemicals are also used medicinally as a diuretic, heart stimulant, blood vessel dilator, and a smooth muscle relaxant. Dogs cannot metabolize theobromine and caffeine as well as people can. This makes them more sensitive to the chemicals’ effects.

Methylxanthines as inducers of pectin lyase in Penicillium griseoroseum cultured on sucrose

Abstract: , 1·0; with the medium containing caffeine or hypoxanthine and yeastpH adjusted to 6·3. Fifty ml of this medium were added to extract. Increases in enzyme activity in the treatments withErlenmeyer flasks (125ml) and treatments consisted of the caffeine and hypoxanthine were 5·2 and 3·7 times, respec-addition to the flasks of yeast extract (YE) and methylxan- tively, the activity measured in the treatment with YE alone.thinesatdifferentconcentrations.Themediawereinoculated Similarly, the addition of both theophylline and YE resultedwith 5˛10

Lipid metabolism promoting composition

Abstract: PROBLEM TO BE SOLVED: To obtain a composition capable of promoting decomposition of fat and effectively reducing body fat by including a xanthine derivative and an amino acid as active ingredients. SOLUTION: This composition has at least one kind of amino acid selected from a xanthin derivative, glycine, histidine, lysine, serine and threonine. The xanthine derivative includes at least one kind of caffeine, theophylline, theobromine, etc. The formulation weight ratio of the amino acid to the xanthine is 1:(0.01-5). The composition can be prepared in the forms of foods and drink and medicines. Daily dose of The medicine is >=100 mg/adult as amino acid and 1-200 mg/adult as xanthine derivative in the case of oral administration. The composition is effective for prevention and dissolution of obesity and more effective in oral administration or ingestion, especially before, after or during exercise.

Thermal properties of zinc butyrate complex compounds

Abstract: The new zinc(II) complexes of general formula Zn(CH3CH2CH2COO)2· nL (whereL = caffeine, nicotinamide, theobromine;n=1 or 2) were prepared and identified.

[Development of syringe-type off line pre-column and simultaneous quantitation of four xanthine derivatives (caffeine, theobromine, theophylline and paraxanthine) in serum].

Abstract: A new syringe-type minicolumn, called Extrashot-Silica (EXS-Silica), containing diatomaceous earth granules was described. The EXS-Silica differs from the conventional pretreatment column. Using the EXS-Silica we can execute the simultaneous extraction-injection to HPLC, column. Therefore, an analysis using the EXS-Silica is an easier and faster method than the general HPLC analysis method. In this study, we carried out the simultaneous determination of four xanthine derivatives, such as caffeine, theobromine, theophylline and paraxanthine, in serum specimens. We used dichloromethane containing 4% ethanol (v/v) for the extraction-injection and water-acetic acid-ethanol-dichloromethane (0.2:0.2:4:95.6, v/v) for the mobile phase of HPLC. The eluent was monitored with a UV detector at 275 nm. A linear relationship between the amount of drug and the peak height was confirmed in the range of 1-40 micrograms/ml for the above-mentioned four xanthine derivatives in the serum. When a 5 microliters aliquot of the serum was subjected to this method, the observed detection limits of the drug were far less than therapeutic concentrations. The analytical accuracy of our method was finally confirmed by comparing the obtained analytical data by the new method with those obtained using the fluorescense polarization immunoassay method. Serum concentrations of theophylline obtained by these two methods correlate satisfactorily. Except for minor modifications in the injector, the existing liquid-chromatographic equipment can be used.