Showing papers on "Theobromine published in 1988"

Caffeine produces contralateral rotation in rats with unilateral dopamine denervation: comparisons with apomorphine-induced responses

Abstract: Like the dopamine agonist apomorphine, the methylxanthines caffeine, theophylline and theobromine produced dose-dependent contralateral rotation in rats with unilateral 6-hydroxydopamine denervation, a response considered to be dependent upon dopamine receptors rendered supersensitive. This response was also observed after the injection of the substances into the denervated striatum. Indeed, intrastriatal administration of caffeine into the dopamine denervated striatum produced, dose-dependently (1.0–50.0 μg/μl), contralateral rotation. However, while apomorphine produced ipsilateral rotation in rats with unilateral striatal kainic acid lesions, a response considered to be dependent upon normosensitive dopamine receptors, neither caffeine nor theophylline produced rotational responses. As for apomorphine, the rotational behaviour elicited by caffeine (15.0 mg/kg SC) and theophylline (25.0 mg/kg SC) was inhibited by the dopamine antagonistscis-(Z)flupentixol, haloperidol and sulpiride. Nevertheless, despite the fact thatcis-(Z)flupentixol was the most potent inhibitor of the caffeine response, no more than 50% inhibition was produced with doses as high as 1.0–10.0 mg/kg SC ofcis-(Z)flupentixol. Pretreatment with alpha methyl-p-tyrosine inhibited the rotational response produced by caffeine in 6-OHDA-lesioned animals, but did not significantly modify the apomorphine response. Furthermore, the benzodiazepine diazepam produced a dose-dependent inhibition of the caffeine rotation, but again, the apomorphine response, although qualitatively modified, was not significantly inhibited.

Increases in plasma concentrations of steroids in the rat after the administration of caffeine: comparison with plasma disposition of caffeine.

Abstract: It was demonstrated that the altered endocrine environment caused by caffeine consumption could be equated with a stress-like pattern of response. A single acute treatment with caffeine (30 or 60 mg/kg) to male rats approximately 85 days old caused plasma concentrations of corticosterone, progesterone, testosterone and Na+ to rise significantly above control values. These changes were evident 3 min after caffeine administration and were maintained for 1-4 h before returning to normal. In animals exposed to daily chronic caffeine treatment for 10 days or more the levels of progesterone fell and Na+ rose significantly compared with control values at 24 h after administration. Following a single treatment of 30 mg/kg, caffeine was detected in blood plasma after 3 min, and reached peak levels by 1 h. After 24 h, less than 2% of the peak levels of caffeine remained. Metabolites of caffeine were detectable within 6 min and reached their peak levels 4 and 12 h later for theophylline and theobromine respectively. It is suggested that high steroid levels may in the long-term cause an altered hepatic clearance pattern affecting both steroid metabolism and caffeine elimination. A preliminary study of the morphology of livers from males chronically exposed to caffeine revealed that the hepatic cells lost cytoplasmic matrix, and that the sinusoids did not show up as clear spaces, compared with those in the controls.

The relaxant and spasmogenic effects of some xanthine derivatives acting on guinea-pig isolated trachealis muscle

Abstract: 1. Caffeine (10 mM)-induced relaxation of guinea-pig isolated trachealis was attenuated and converted to a small spasmogenic response on cooling to 22 degrees C. The relaxant response was restored on rewarming to 37 degrees C and was abolished by indomethacin (2.8 microM). Cooling to 22 degrees C in the presence of indomethacin revealed spasmogenic responses to caffeine which were abolished on rewarming to 37 degrees C. 2. Trachealis treated with indomethacin (2.8 microM) was repeatedly dosed with acetylcholine (ACh, 10 microM). Caffeine (1 or 10 mM), added as each ACh-induced spasm reached equilibrium, transiently augmented but then suppressed the spasm. On cooling from 37 degrees C to 12 degrees C, the increment in spasm evoked by caffeine increased relative to the spasm evoked by ACh. 3. Trachealis treated with indomethacin (2.8 microM) was repeatedly dosed with caffeine (10 mM). At 37 degrees C caffeine had little effect but it caused spasm when the tissue was cooled to 32 degrees C. Spasm amplitude increased as cooling progressed to 12 degrees C. Similar results were obtained with caffeine (1 mM). 4. At 37 degrees C, caffeine, enprofylline, 1,3,7,9-tetramethylxanthinium (TMX), theobromine, theophylline, xanthine and forskolin each caused concentration-dependent suppression of tracheal tone. Among the xanthine derivatives the rank order of potency was enprofylline greater than theophylline greater than caffeine greater than theobromine greater than xanthine greater than TMX. 5. In trachealis treated with indomethacin (2.8 microM) and maintained at 12 degrees C, the xanthines each caused concentration-dependent spasm. The rank order of potency was theobromine greater than or equal to theophylline greater than or equal to caffeine greater than or equal to enprofylline greater than xanthine greater than TMX. Forskolin was devoid of spasmogenic activity. 6. Trachealis treated with indomethacin (2.8 microM) and maintained at 12 degrees C, was repeatedly dosed with either caffeine (10 mM) or potassium chloride (KCl, 40 mM). Caffeine-induced spasm was attenuated in a Ca2+-free medium containing EGTA (2 mM), modestly at first but subsequently more profoundly. KCl did not evoke spasm at 12 degrees C but at 37 degrees C the KCl-induced spasm was virtually abolished at its first trail in the Ca2+-free, EGTA-containing medium. 7. It is concluded that caffeine, other alkylated xanthines and xanthine itself share a spasmogenic action in guinea-pig isolated trachealis which is best observed when the tissue is treated with indomethacin (2.8 microM) and maintained at 12 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolism and Analysis of Caffeine and Other Methylxanthines in Coffee, Tea, Cola, Guarana and Cacao

Abstract: The widespread natural occurrence of purine alkaloids — caffeine and other methylxanthines such as theobromine and theophylline (Fig. 1) — in a variety of plants undoubtedly played a major role in the long-standing popularity of caffeine-containing products, especially nonalcoholic beverages and foods (coffee, tea, soft drinks, cocoa and chocolate products, etc.). More than 60 plant species throughout the world have been identified as containing caffeine; the more common are from the genera Coffea, Camellia, Cola, Paullinia, Ilex, and Theobroma (Kihlman 1977). It is not claimed that this summary is complete, since almost every year corrections are made or new plants are found to contain caffeine; for instance, the occurrence of caffeine in citrus flowers and leaves has been reported recently (Stewart 1985). Further, the list of purine alkaloids has recently been extended by the discovery of three methyluric acids (Fig. 1) in the genus Coffea (Pe-termann and Baumann 1983).

Caffeine and Its Dimethylxanthine Metabolites in Two Cases of Caffeine Overdose: A Cause of Falsely Elevated Theophylline Concentrations in Serum

Abstract: Two children ingested over-the-counter medications containing caffeine, resulting in significant caffeine overdose. Measured concentrations of caffeine were as high as 176 and 128 mg/L. We have described the elimination of caffeine and its dimethylxanthine metabolites, paraxanthine, theophylline, and theobromine in these cases. The apparent theophylline concentrations determined after caffeine ingestion were dependent upon the method of measurement. Use of one published reversed-phase HPLC method, which does not separate theophylline from paraxanthine, resulted in overestimation of theophylline by 225 to 513%. Use of an enzyme immunoassay procedure resulted in a lesser degree of overestimation (142-383%), which was due, in part, to cross-reactivity with extremely high concentrations of caffeine and paraxanthine. The measurement of caffeine concentrations in the management of caffeine overdose is of limited clinical usefulness; likewise, measurement of theophylline concentrations is generally not indicated, and may be misleading unless a highly specific assay is used.

Pharmacology of Calcium Uptake and Release from the Sarcoplasmic Reticulum: Sensitivity to Methylxanthines and Ryanodine

Abstract: A number of plant alkaloids affect the contraction of striated muscles, amongst these the methylxanthines and ryanodine have been widely used as their action may throw light upon the role of the specialised endoplasmic reticulum of muscle in the excitation-contraction-relaxation sequence The methylxanthines popularly used, caffeine, theobromine, theophylline and paraxanthine have a common chemical structure consisting of a double ring where a pyramidine and an imidazole combine to give the xanthine structure (Fig 1 a) Ryanodine is a more complex molecule, incorporating a single nitrogen-containing pyrrole ring (Fig 1 b)

Determination of Methylxanthine Stimulants in Urine of Racing Greyhounds by High-Performance Liquid Chromatography. Resolution of a Contested Drug Administration Case

Abstract: Results of urine drug analyses for three racing greyhounds that tested positive for caffeine in this laboratory were contested by the animal trainer, who asserted that positives were achieved from deliberate chocolate feeding by a rival kennel. The metabolism and excretion of methylxanthines was examined by high-performance liquid chromatography of extracts of the urine of racing greyhounds force-fed either caffeine (No Doz) or chocolate (Hersheys chocolate drops). Samples from untreated animals served as controls. Study results showed that test animals fed chocolate could be very easily distinguished from those fed caffeine. While the former animals exhibited a prominent theobromine peak with trace amounts of caffeine and theophylline, the caffeine-treated animals gave a prominent caffeine peak with moderate theophylline levels and almost nondetectable theobromine amounts. When these results were compared with the results from the positive authentic racing animals, chocolate feeding was clearly ruled out as an alternative to caffeine administration.

Interaction of caffeine with acetaminophen in mice: schedule dependency of the antagonism by caffeine of acetaminophen hepatotoxicity and the effects of caffeine metabolites, allopurinol, and diethyl ether.

Abstract: Administration of caffeine (CAF) to mice as early as 6 hr prior to injection of a hepatotoxic but nonlethal dose of acetaminophen (ACM) significantly antagonized the hepatotoxic action of ACM as judged by serum levels of alanine aminotransferase (ALT) activity. Administration of CAF after ACM produced complete antagonism only when CAF was given no later than 1 hr after ACM. Administration of CAF daily for 3 days prior to injection of ACM enhanced ACM toxicity markedly, but little or no toxicity ensued when CAF-pretreated mice received ACM followed immediately by CAF. The four primary metabolites of CAF, 1,3-dimethylxanthine (theophylline), 3,7-dimethylxanthine (theobromine), 1,7-dimethylxanthine (paraxanthine), and 1,3,7-trimethyluric acid were effective and virtually complete antagonists of ACM-induced hepatotoxicity when given immediately after ACM, as were the secondary metabolites, 1-methylxanthine and 1,3-dimethyluric acid. Allopurinol, which reduces theophylline clearance, increases the rate of oxidative N-demethylation of theophylline to 1-methylxanthine, and inhibits conversion of 1-methylxanthine to 1-methyluric acid, was also a dose-dependent antagonist of ACM-induced hepatotoxicity. The hepatotoxic response of mice to ACM is exaggerated by a brief period of diethyl ether anesthesia; CAF given immediately after ACM to previously anesthetized mice suppressed this response and maintained serum ALT levels at control values. It is suggested that CAF and its primary metabolites compete with ACM for biotransformation by the cytochrome P-450 mixed function oxidase system, thereby reducing the rate of formation of the hepatotoxic ACM metabolite.

CHAPTER 23 – Purines

Abstract: Publisher Summary Purine alkaloids are widely distributed within the plant kingdom. However, their occurrence is limited to dicotyledonous species, preferentially in tropical and subtropical climates. Caffeine and theobromine, methylated derivatives of xanthine, are generally the main purine alkaloids and are regularly accompanied in low concentrations by the two methylxanthines theophylline, paraxanthine, as well as by methylated uric acids such as theacrine. Purine alkaloids are, botanically and geographically, a widespread component of human diet. Optimum environmental conditions and medium composition allow good growth and alkaloid production rates in both callus and suspension cultures. Purine alkaloid system is a suitable model for investigating in vitro production of secondary compounds. The key advantages are: (a) the presence of only two alkaloids that may easily be analyzed quantitatively by high performance liquid chromatography; (b) selection of cell lines with relatively stable productivity on the basis of cell aggregation characteristics; and (c) a large body of background information concerning physiological and ecological properties of purine alkaloids that is essential in developing new strategies for synthesis of natural products by means of tissue culture biotechnology. Purine alkaloid formation accelerates during the cultivation time, which means that most of the final amount of purine alkaloids is synthesized after the exponential period of growth.