Theobromine

About: Theobromine is a research topic. Over the lifetime, 1137 publications have been published within this topic receiving 29723 citations. The topic is also known as: 3,7-Dimethylxanthine & Theobromin.

Influence of some common methylxanthines on contractile responses and calcium mobilization of ileal, vas deferens and bladder smooth muscle

Abstract: Caffeine and theophylline (0.1-5.0 mM) relaxed rat ileal muscle and reduced spontaneous rhythmicity. They inhibited the K-induced tonic contractures of rat vas deferens and bladder muscle strips but were without significant effect on the phasic responses to K. Theobromine (1.0-2.5 mM) induced contractures in ileal muscle and enhanced both the phasic and tonic components of K-induced contractures in vas deferens and bladder muscle strips. Theophylline and caffeine inhibited by varying degrees the 45Ca efflux from ileal, vas deferens and bladder muscle strips during the slow intracellular phase, but theobromine significantly stimulated 45Ca slow compartment efflux in all three types of muscle. Caffeine and theophylline both depressed, to varying degrees, the 45Ca influx into all three muscles while theobromine stimulated 45Ca influx in all cases. Caffeine and theophylline were either without much effect or slightly stimulated calcium binding by microsomes and mitochondria isolated from ileum, vas deferens and bladder, while theobromine significantly inhibited calcium binding by both sub-cellular fractions in all three muscles. The inhibitory action of caffeine and theophylline on these muscles appears to be due to inhibition of calcium influx coupled with some stimulation of intracellular binding. Theobromine's excitatory action appears to be related to stimulation of calcium influx and inhibition of cellular calcium binding.

Effects of baicalin on oral pharmacokinetics of caffeine in rats.

Abstract: Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.

Pharmacokinetics of caffeine and its demethylated metabolites in lactating adult rabbits and neonatal offspring. Predictions of breast milk to serum concentration ratios.

Abstract: The purpose of this study was to assess the pharmacokinetics of caffeine and its metabolites in the lactating rabbit and suckling pup. The ability of a diffusional model to predict milk-to-serum drug concentration ratios (M/S) observed in vivo from in vitro experiments was established. The distribution into milk of caffeine, paraxanthine, theobromine, and theophylline was measured in lactating New Zealand White rabbits following an iv bolus dose of caffeine (5 mg/kg). M/S ratios were determined in vivo (M/Sobs; caffeine = 0.875 +/- 0.052; paraxanthine = 0.358 +/- 0.019; theobromine = 0.829 +/- 0.038; and theophylline = 0.412 +/- 0.054) under single dose conditions using area under the milk and serum concentration-time profiles. Predicted M/S values (M/Spred; caffeine = 0.797 +/- 0.040; paraxanthine = 0.316 +/- 0.029; theobromine = 0.692 +/- 0.062; and theophylline = 0.385 +/- 0.039) were calculated from in vitro measurements of the unbound fractions of drug in skim milk and serum (fm and fs, respectively), the skim-to-whole milk drug concentration ratio (S/W), milk and serum pH, and the pKa of the model compound. The pharmacokinetic profile of caffeine in the suckling pup following iv bolus administration (5 mg/kg) was more prolonged compared with adult rabbits. The mean systemic clearance of total caffeine (CIs) in the adults and the pups was 3.83 +/- 1.94 and 1.14 +/- 0.80 ml/min/kg, respectively. The mean unbound systemic clearance (CIs,u) for caffeine was 5.09 +/- 2.60 ml/min/kg in the adults and 1.41 +/- 0.71 ml/min/kg in the pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of xanthine derivatives on cough and airway reactivity in guinea pigs

Abstract: Xanthine derivatives may inhibit phosphodiesterases without selective action on their single isoforms. In this study, effects of theophylline and theobromine on cough and airway reactivity were evaluated in awake guinea pigs using double-chamber whole body plethysmograph. Pre-treatment with theophylline and theobromine (10 mg/kg, i.p.) decreased the number of cough efforts evoked by inhalation of citric acid aerosol (0.6 mol/l) in both healthy and ovalbumin-sensitized animals. Theophylline and theobromine decreased in vivo airway reactivity, i.e., specific airway resistance measured after nebulization of citric acid and histamine aerosol (10(-6) mol/l), only in ovalbumin-sensitized animals, whereas in vitro reactivity to cumulative doses of histamine and acetylcholine (10(8)-10(-3) mol/l) measured in organ chambers significantly decreased in both healthy and ovalbumin-sensitized animals, with more pronounced effect in the latter group. In conclusion, administration of theophylline and theobromine influenced the cough and airway reactivity in ovalbumin-sensitized guinea pigs, indicating the anti-inflammatory potential of xanthine derivatives.