Showing papers on "Theobromine published in 1994"
TL;DR: Johannsen et al. as discussed by the authors used a static analytical method with direct coupling of an equilibrium cell to a supercritical fluid Chromatographic (SFC) system to determine the solubilities of the xanthines caffeine, theophylline and theobromine in supercritical carbon dioxide.
115 citations
TL;DR: It is suggested that commonly consumed cocoa products contain behaviorally active doses of caffeine and possibly theobromine, as well as other drugs, which are known to produce discriminative effects in humans.
Abstract: Theobromine versus placebo discrimination and caffeine versus placebo discrimination were studied in two consecutive experiments in seven volunteers who abstained from methylxanthines. Daily sessions involved PO double-blind ingestion of two sets of capsules sequentially, one of which contained drug and the other placebo. Subjects attempted to identify, and were later informed, which set of capsules contained the drug. In each experiment subjects were exposed to progressively lower doses. Five subjects acquired the theobromine discrimination; the lowest dose discriminated ranged from 100 to 560 mg. All seven subjects acquired the caffeine discrimination; the lowest dose discriminated ranged from 1.8 to 178 mg. A final experiment evaluated subjective effect ratings following 560 mg theobromine, 178 mg caffeine and placebo, which were administered double-blind in capsules once daily, five times each in mixed sequence. Caffeine produced changes in both group and individual ratings (e.g. increased well-being, energy, social disposition and alert). Theobromine did not produce changes in group ratings but changed ratings in some subjects. Across subjects, sensitivity to caffeine discriminative effects in the discrimination experiment correlated significantly with the number and magnitude of caffeine subjective effects in the final experiment. This study documents modest discriminative effects of theobromine in humans, but the basis of the discrimination is unclear. This study suggests that commonly consumed cocoa products contain behaviorally active doses of caffeine and possibly theobromine.
108 citations
TL;DR: The delay in the maturation of N-1 compared with N-3 and N-7-demethylation is in agreement with previous in vivo data, and the difference in maturational profiles of each metabolic pathway suggests that the reactions depend on different isoenzymes.
Abstract: 1. Caffeine metabolism was studied in human liver microsomes from foetuses (n = 10), neonates (n = 10), infants (n = 9) and adults (n = 5). Caffeine and its metabolites, 1-3-7-trimethyluric acid, paraxanthine, theophylline and theobromine, were assayed by h.p.l.c. Methoxyresorufin-O-demethylase activity (MEROD) was determined and immunoquantifiable levels of CYP1A2 were measured. 2. The formation of the dimethylxanthines by N-3, N-7 or N-1-demethylation was significantly less in foetuses, neonates and infants than in adults, as shown previously in vivo. The formation of 1-3-7-trimethyluric acid (C-8-hydroxylation) was not significantly different between age groups. The production of total dimethylxanthines, paraxanthine and theophylline increased significantly with age within the neonate-infant group over at least the 0-300 day range (rs = 0.739, 0.667, 0.682, respectively). These data differ from those reported in vivo which suggested that N-3 and N-7-demethylations matured at about 120 days. The difference in maturational profiles of each metabolic pathway suggests that the reactions depend on different isoenzymes. The delay in the maturation of N-1 compared with N-3 and N-7-demethylation is in agreement with previous in vivo data. 3. In the neonate-infant group, only N-3-demethylation correlated with both MEROD activity (rs = 0.681; P < 0.05) and CYP1A2 microsomal concentration (rs = 0.454; P approximately 0.05), suggesting that, as in adults, this reaction depends on CYP1A2. 4. In the foetal samples, the production of total dimethylxanthines, paraxanthine and theobromine decreased significantly (rs = -0.879, -0.767, -0.708, respectively) with increasing gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)
105 citations
TL;DR: The seeds and leaves of nine Herrania and 11 Theobroma species were examined for their purine alkaloid content as mentioned in this paper, and Tetramethyl urate was the principal purine acid present.
40 citations
TL;DR: Data on the purification and N -terminal sequence of S -adenosyl- l -methionine: theobromine 1- N -methyltransferase (STM) is presented.
39 citations
TL;DR: A monooxygenase specific for theobromine demethylation was purified from the cell-free extract of Pseudomonas putida No. 352 to homogeneity and appears to be demethylated to 7-methylxanthine at least by two enzymes.
Abstract: A monooxygenase specific for theobromine demethylation was purified from the cell-free extract of Pseudomonas putida No. 352 to homogeneity. Caffeine appears to be demethylated to 7-methylxanthine at least by two enzymes, caffeine demethylase and theobromine demethylase. The latter is sensitive to Zn2+ and possibly caused an accumulation of theobromine in P. putida No. 352.
39 citations
TL;DR: The extent of degradation of adenine nucleotides by the conventional purine catabolic pathway was low in both leaves and the level of radioactivity taken up by the young leaves was low.
30 citations
Journal Article•
TL;DR: It is demonstrated that omeprazole increases the metabolism of caffeine, especially N-1 and N-3 demethylation pathways, after 28 days of treatment with omepazole, and suggested that omEPrazole, when used for this period, is an inducer of hepatic cytochrome P4501A2.
29 citations
TL;DR: In this paper, the absorption and fluorescence spectra of aqueous solutions of xanthine, caffeine, theophylline and theobromine have been studied at different pH.
24 citations
TL;DR: The xanthine content of guaraná powder was determined, in addition to its clearance time in horses, and in urine it was possible to detect TB and TP up to 13 d and CF up to 9 d after the administration of guyaná powder.
Abstract: The seeds of Guarana are rich in xanthines and are used for the preparation of guarana powder which is very commonly given to horses as a ‘tonic’ in Brazil. In this paper, the xanthine content of guarana powder was determined, in addition to its clearance time in horses. Thin-layer chromatography was used as a screening procedure and high-performance liquid chromatography was performed to quantify the drugs in both the powder and urine samples. The guarana powder was found to contain 2.16, 1.10 and 36.78 mg g–1 of theobromine (TB), theophylline (TP) and caffeine (CF), respectively, and in urine it was possible to detect TB and TP up to 13 d and CF up to 9 d after the administration of guarana powder.
01 Jan 1994
TL;DR: In the mate plant (Ilex paraguaryensis Lamb), the levels of theobromine and theophylline were found to be higher in younger tissues.
Abstract: Caffeine, theobromine and theophylline contents were determined in developing and old leaves, bark, wood, and immature and mature fruits of the mate plant (Ilex paraguaryensis Lamb.). Caffeine and theobromine levels were always higher in younger tissues. Analysis in partially shaded plant showed a proportional increase of theobromine when compared to caffeine. Theophylline was not detected in bark, wood and fruits. Additional index terms: Caffeine, metabolism, mate plant, methylxanthines.
TL;DR: The results support Sertoli cells as the primary target cells of theobromine toxicity in rats treated with cocoa extract and could account for the lower toxicity in these animals.
TL;DR: Caffeine biotransformation was demonstrated in three novel human hepatocyte cell lines established from normal liver tissue and cultured continuously for 19 to 30 months, demonstrating in vitro metabolism of caffeine observed in man in vivo.
TL;DR: In rats with liver damage, the production of 3 metabolites of caffeine in addition to the only metabolite of trimethadione after intravenous administration of probe drugs were significantly reduced compared to those of controls, suggesting that each probe drug is useful in evaluating drug-oxidizing capacity in liver disease.
Abstract: We investigated the possibility of predicting liver damage from changes in the serum concentrations of caffeine (10 mg/kg), lidocaine (4 mg/kg) and trimethadione (4 mg/kg), which are metabolized catalysed by different cytochrome P450 (P450) and/or are dependent on blood flow, in rats with carbon tetrachloride (CCl4: 0.25 ml/kg)-induced liver injury using a strategy referred to as a “cocktail” study. These 3 probe drugs were simultaneously administered intravenously. The half-lives (t1/2) of caffeine, lidocaine and trimethadione were significantly longer in the CCl4-treated group than in oil-treated controls, but no significant differences were observed in mean apparent volumes of distribution (Vd). Serum total body clearance (CL) values of all three drugs were markedly reduced in CCl4-treated animals. In rats with liver damage, the production of 3 metabolites (theobromine, paraxanthine and theophylline) of caffeine in addition to the only metabolite (dimethadione) of trimethadione after intravenous administration of probe drugs were significantly reduced compared to those of controls. These findings suggest that each probe drug, metabolized by different or partially overlapping P450, is useful in evaluating drug-oxidizing capacity in liver disease.
TL;DR: It is concluded that many of the differences in the effects of these methylxanthines can be attributed to differences in membrane permeability due to Differences in oil:water partition.
Abstract: 1. The effects of caffeine and other methylxanthines were investigated on intracellular calcium concentration ([Ca2+]i) and contraction in rat isolated ventricular myocytes. The use of the fluorescent indicator, Indo-1, allowed simultaneous measurement of [Ca2+]i and the intracellular concentration of the methylxanthines. 2. Rapid application of caffeine (10 mM) produced a transient rise of [Ca2+]i which decayed to resting levels. This was accompanied by a transient contraction which decayed to a level above baseline. The addition of theophylline also produced a transient increase of [Ca2+]i. However, following the initial transient, contraction decayed before redeveloping to a maintained level. 3. Direct measurements showed that [caffeine]i rose more quickly than did [theophylline]i. The slower rise of [theophylline]i was associated with a delay in the increase of [Ca2+]i. At lower concentrations of the methylxanthines, theophylline was less effective than caffeine at initiating Ca release. The rate of entry of theobromine was similar to that of theophylline. 4. Isocaffeine did not produce a rise of [Ca2+]i. The rate of rise of [isocaffeine]i was much slower than that of either caffeine or theophylline. 5. Measurements of the oil:water partition coefficient showed that the order of relative partitioning into oil was: caffeine > theophylline > theobromine > isocaffeine. This is similar to the order of rate of entry into the cell. 6. We conclude that many of the differences in the effects of these methylxanthines can be attributed to differences in membrane permeability due to differences in oil:water partition.
TL;DR: In this paper, the interaction of the theophylline, theobromine, and 3-methyluracil rings of these compounds was studied based on their 1H NMR spectra, and stacking of the two purine rings of 7,7′-(α,ω-alkanediyl)bis[theophyllines] was observed.
Abstract: The treatment of theophylline, theobromine, and 3-methyluracil with X(CH2)nX (X = Br or I, n = 1—12) in N,N-dimethylformamide containing sodium hydride gave the corresponding 7,7′-(α,ω-alkanediyl)bis[theophylline], 1,1′-(α,ω-alkanediyl)bis[theobromine], and 1,1′-(α,ω-alkanediyl)bis[3-methyluracil]. The interaction of the theophylline, theobromine, and 3-methyluracil rings of these compounds was studied based on their 1H NMR spectra, and stacking of the two purine rings of 7,7′-(α,ω-alkanediyl)bis[theophylline] was observed.
TL;DR: The use of an adsorption column employing the hydrophobic resin Amberlite XAD-4 increased alkaloid production 1.4-fold compared to the culture with no removal treatment and the negative effects of hormone removal by the adsorbent were canceled out by the addition of fresh medium.
Patent•
05 Dec 1994
TL;DR: Theophylline, theobromine and derivatives and salts thereof are used for the chronic prophylactic treatment of mild asthma as discussed by the authors, and they are used in the treatment of lung cancer.
Abstract: Theophylline, theobromine and derivatives and salts thereof are used for the chronic prophylactic treatment of mild asthma.