Showing papers on "Theobromine published in 1983"

Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines.

Abstract: 1. The potencies of caffeine and related methylxanthines as adenosine antagonists were assessed with respect to three apparent subtypes of adenosine receptors in rat brain preparations: (i) the A1-adenosine receptor which binds with a very high affinity the ligand [3H]cyclohexyladenosine (KD, 1 nM) in rat brain membranes; (ii) a ubiquitous low-affinity A2-adenosine receptor which activates cyclic AMP accumulation in rat brain slices—this A2-adenosine system exhibits an EC50 for 2-chloroadenosine of about 20µM; and (iii) a relatively high-affinity A2-adenosine receptor which activates adenylate cyclase in rat striatal membranes—this A2-adenosine system exhibits an EC50 for 2-chloroadenosine of about 0.5µM and is present in striatal but not in cerebral cortical membranes. 2. The rank order of potency for methylxanthines versus binding of 1 nM [3H]cyclohexyladenosine in membranes from eight rat brain regions is theophylline (IC50, 20–30µM) > paraxanthine (IC50, 40–65µM) > caffeine (IC50, 90–110µM) > theobromine (IC50, 210–280µM). There thus appears to be little difference in A1-receptors in different brain regions in terms of interaction with these methylxanthines. 1-Methylxanthine is more potent than caffeine in rat cerebral cortical membranes, while 3-methylxanthine and 7-methylxanthine are less potent than caffeine. 3. The rank order of potency for methylxanthines versus activation of cyclic AMP accumulation by 50µM 2-chloroadenosine in rat striatal slices is theophylline (IC50, 60µM) > paraxanthine (IC50, 90µM) > caffeine (IC50, 120µM) » theobromine (IC50, > 1000µM). Similar potencies pertain in cerebral cortical slices. 4. The rank order of potency of methylxanthines versus activation of adenylate cyclase by 1µM 2-chloroadenosine in rat striatal membranes is theophylline (IC50, 20µM) > paraxanthine (IC50, 40µM) > caffeine (IC50, 80µM) » theobromine (IC50, > 1000µM). 5. Caffeine and other methylxanthines, thus, antagonize effectively both A1- and A2-adenosine receptors in brain perparations. Theobromine appears less effective versus A2-receptors than versus A1-receptors. Caffeine exhibits aKi value of about 50µM at the very high-affinity A1-binding sites, aKi value of about 30µM at the low-affinity A2-adenosine site in brain slices, and aKi value of about 27µM at the high-affinity A2-adenosine site in striatal membranes. The functional significance of antagonism of such adenosine receptors by caffeinein situ will depend both on the local levels of adenosine and on the affinity for adenosine for the receptor, since antagonism by xanthines is competitive in nature. In addition, the functional significance of xanthine action will depend on the degree of inhibition of adenosine input which is required to alter the output signal. For a stimulatory input to adenylate cyclase via an A2-adenosine receptor, profound antagonism by methylxanthines is probably required to alter the cyclic AMP-mediated output signal, while for inhibitory input to adenylate cyclase via an A1-adenosine receptor, presumably a lesser degree of antagonism by methylxanthines may be required to alter the cyclic AMP-mediated output signal.

Disposition of caffeine and its metabolites in man.

Abstract: The disposition of caffeine and its metabolites was studied in six healthy subjects by use of sensitive and specific assays. The primary degradation of caffeine in man was found to be N-demethylation and/or ring oxidation to theophylline, paraxanthine, theobromine and 1,3,7-trimethyluric acid. These compounds were further degraded to dimethylated uric acids, monomethylxanthines and monomethyluric acids. About 3 and 6% of the drug was converted to theophylline and theobromine, respectively. The elimination of paraxanthine after its formation did not follow linear kinetics. A large urine recovery of 1-methylxanthine after caffeine administration in comparison with the amount recovered after administration of theophylline suggests an inhibitory effect on the degradation of this metabolite by either caffeine itself or another metabolite of caffeine. Caffeine and its primary metabolites, dimethylxanthines, were extensively reabsorbed in the renal tubule. Their renal clearances were highly urine flow-dependent and their urinary excretion varied with urine output during the study. About 70% of the dose was recovered in the urine. Postulated degradation pathways of caffeine are discussed.

Comparative Inhibiting Effects of Methylxanthines on Urethan-induced Tumors, Malformations, and Presumed Somatic Mutations in Mice

Abstract: The inhibiting effects of methylxanthines on urethan-induced lung tumors, malformations, and presumed somatic mutations in mice were studied to determine the contribution of mutational and physiological changes to chemically induced neoplasia and malformation. When young adult or pregnant ICR/Jc1 mice were treated with urethan and then methylxanthines were given, caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) greatly suppressed urethan-induced tumorigenesis and teratogenesis, while theophylline (1,3-dimethylxanthine) did not. Of the three monomethylxanthines (methylated at positions 1, 3, or 7), 7-methylxanthine was most effective for inhibiting tumors and malformations, indicating that the methyl group at position 7 is most active. Contribution of cyclic adenosine 3′:5′-monophosphate was ruled out, since urethan-induced tumorigenesis and teratogenesis were not affected by theophylline which elevates the cellular level of cyclic adenosine 3′:5′-monophosphate by inhibiting phosphodiesterase more effectively than caffeine does; instead, tumorigenesis and teratogenesis were greatly inhibited by theobromine and 7-methylxanthine, which do not alter the level of cyclic adenosine 3′:5′-monophosphate. To test the mutational origin of cancer and malformation, the effects of caffeine on urethan induction of somatic mutations in PT × HT F1 mice were examined, because caffeine is known to inhibit ultraviolet- and 4-nitroquinoline 1-oxide-initiated mutagenesis in Escherichia coli by inhibiting error-prone repair. In mice, however, caffeine did not inhibit urethan-induced somatic mutations. Furthermore, theophylline, an inhibitor of error-prone repair, did not reduce the yields of tumors and malformations. Antineoplastic and antiteratogenic effects of caffeine may be caused not by the inhibition of the mutational change but by the inhibition of the subsequent process for expressing tumors and malformations.

Metabolic Relations between Methylxanthines and Methyluric Acids in Coffea L.

Abstract: Metabolism of purine alkaloids in the leaves of Coffea dewevrei De Wild et Durand var excelsa Chev, Coffea liberica Bull ex Hiern and Coffea abeokutae Cramer was studied by analyzing leaf discs collected during vegetative development and by feeding the following radioactive tracers: [(14)C]theobromine, [(14)C]caffeine, and [(14)C]theacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites were quantitatively and qualitatively determined. All three species convert the precursors to the same radioactive products, and proceed through the same four maturity stages characterized by the alkaloid accumulation pattern and by a particular transformation potency: (stage 1) young plant accumulating caffeine, transforms theobromine to caffeine; (stage 2) caffeine is gradually replaced by theacrine, theobromine and caffeine are converted to theacrine; (stage 3) theacrine disappears whereas liberine (O(2), 1,9-thrimethyluric acid) accumulates, theacrine is metabolized to liberine; (stage 4) branched-out plant containing liberine but no theacrine, caffeine is converted rapidly to liberine via theacrine. Methylliberine (O(2),1,7,9-tetramethyluric acid), presumably the direct precursor of liberine, is occasionally found in low concentrations at stage 3 and 4.The collective term ;liberio-excelsoid' introduced by geneticists for the numerous races or species of Pachycoffea is in accordance with the phytochemical equality found in this work.

Metabolic Relations between Methylxanthines andMethyluric Acids inCoffea L.

Abstract: Metabolism ofpurine alkaloids intheleaves ofCoffea dewevrei De WildetDurand varexcelsa Chev, Coffea liberica BullexHiern and Coffea abeokuftae Cramer wasstudied byanalyzing leaf discs collected during vegetative development andbyfeeding thefollowing radioactive tracers: I4CQtheobromine, I"Clcaffeine, andI'Qtheacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites werequantitatively and qualitatively determined. Allthree species convert theprecursors tothe sameradioactive products, andproceed through thesamefour maturity stages characterized bythealkaloid accumulation pattern andbya particular transformation potency: (stage 1)youngplant accumulating caffeine, transforms theobromine tocaffeine; (stage 2)caffeine isgradually replaced bytheacrine, theobromine andcaffeine areconverted to theacrine; (stage 3)theacrine disappears whereas liberine (0(2) 1,9thrimethyluric acid) accumulates, theacrine ismetabolized toliberine; (stage 4)branched-out plant containing liberine butnotheacrine, caffeine isconverted rapidly toliberine viatheacrine. Methylliberine (0(21I,7,9tetramethyluric acid) presumably thedirect precursor ofliberine, is occasionally found inlowconcentrations atstage 3and4. Thecollective term'fiberio-excelsoid' introduced bygeneticists forthe numerous races orspecies ofPachycoffea isinaccordance withthe phytochemical equality found inthis work.

Neuroendocrine effects of caffeine. II. Effects on thyrotropin and corticosterone secretion.

Abstract: Caffeine injected i.p. to rats decreased serum thyrotropin and markedly increased serum corticosterone with ED50 values of 40 to 50 mg/kg. Adrenalectomy did not affect the response of thyrotropin to caffeine. Theophylline was as potent as caffeine in inhibiting thyrotropin and stimulating corticosterone secretion; theobromine and paraxanthine were less potent, but their own serum concentrations were also lower. One week of once-daily injections of 50 mg/kg of caffeine produced tolerance to its effects on thyrotropin and corticosterone. The lowest caffeine dose to produce tolerance to a 50-mg/kg challenge dose was 25 mg/kg. Adenosine receptor agonists did not affect serum thyrotropin nor did they block the caffeine-induced decrease in serum thyrotropin. Blockade of the hypothermic effect of caffeine did not alter the effect of caffeine on serum thyrotropin. Similarly, the caffeine-induced decrease in serum thyrotropin was additive to the decrease produced by placing rats in a warm environment or to the increase in serum thyrotropin produced by placing them in the cold. Deviating from the stress-like pattern of increased corticosterone and decreased thyrotropin, caffeine did not affect prolactin secretion in ovariectomized rats with or without estrogen pretreatment.

Theobromine kinetics and metabolic disposition

Abstract: Metabolism and kinetics of a single oral dose of 30 μCi 8-14C-theobromine with 10 mg/kg theobromine sodium acetate were studied in six healthy, nonmedicated, nonsmoking men after 14 days' abstention from all methylxanthine sources. Identification and quantitation of metabolites in plasma and urine both by HPLC and by thin-layer chromatography coupled with radiography indicated that theobromine was predominant in plasma. For urine, both methods identified theobromine as well as 7-methylxanthine, 7-methyluric acid, 3-methylxanthine, 6-amino-5[N-methylformylamino]-l-methyluracil, and a small amount of 3,7-dimethyluric acid as the metabolites of theobromine. All administered radioactivity was recovered in urine and no polar metabolites could be detected. Analysis of the urinary excretion data by the sigma-minus method allowed calculation of the apparent first-order rate constants for production of 7-methylxanthine, 7-methyluric acid, 3-methylxanthine, 3,7-dimethyluric acid, and 6-amino-5[N-methylformylamino]-l-methyluracil. Clinical Pharmacology and Therapeutics (1983) 34, 546–555; doi:10.1038/clpt.1983.212

Determination of purine alkaloids and trigonelline in instant coffee and other beverages using high performance liquid chromatography.

Abstract: A simple, rapid high performance liquid chromatography method is reported for the simultaneous analysis of trigonelline and caffeine (1,3,7-trimethylxanthine) in coffee, and theobromine (3,7-dimethylxanthine) and caffeine in samples of cocoa, drinking chocolate, tea and cola. Chromatography was carried out on Spherisorb-ODS columns with gradient elution. The eluate was monitored at 272 nm with an ultraviolet spectrophotometer and quantification was achieved with external standards. Results for different brands of instant coffees, one decaffeinated coffee, and for samples of cocoa, drinking chocolate, tea and cola are reported.

N-methyltransferase activities in suspension cultures of Coffea arabica L.

Abstract: Suspension cultures of Coffea arabica L. are a useful source for methyltransferase preparations of high activity catalysing the transfer of methylgroups from S-adenosyl-L-methionine to 7-methylxanthine and to theobromine producing theobromine and caffeine respectively. Surprisingly, these enzyme activities are not correlated with the availability of precursors during a culture cycle. They are highest in the growth phase when supply of precursors is reduced. Mixed substrate experiments and time dependent changes in the enzyme activity ratio provide indirect evidence for the existence of two separate enzymes catalysing the final methylations in caffeine biosynthesis.

Inhibition by xanthine derivatives of adenosine receptor‐stimulated cyclic adenosine 3′, 5′‐monophosphate accumulation in rat and guinea‐pig thymocytes

Abstract: The effect of stable adenosine analogues, including adenosine 5'-N-ethylcarboxamide (NECA) and N6-L-phenylisopropyl-adenosine (L-PIA), were studied on cyclic adenosine 3', 5'-monophosphate (cyclic AMP) accumulation in rat and guinea-pig thymocytes NECA was approximately 10 times more potent than L-PIA, in thymocytes from both species D-PIA was more potent in guinea-pig than in rat thymocytes The effect of a number of adenosine analogues followed the order: NECA greater than 2-chloro-adenosine greater than L-PIA greater than N6-cyclohexyl-adenosine (CHA), an order of potency characteristic for adenosine receptors of the A2-subtype Thymocytes may be used as a model system to study the pharmacology of such receptors Several xanthines were studied as antagonists of the NECA (1 microM)-induced cyclic AMP accumulation The order of potency was: 1,3-diethyl-8-phenylxanthine greater than 8-phenyl-theophylline greater than IBMX = 8-p-sulphophenyltheophylline = verrophylline greater than theophylline greater than caffeine greater than enprofylline greater than theobromine greater than pentoxiphylline The pA2 value for 8-phenyltheophylline was 035 microM, and the antagonism was shown to be competitive The order of potency of the xanthine is virtually identical to that found earlier in several other systems in which the receptors are of the A1-subtype None of the xanthine derivatives tested thus seem to discriminate between A1 and A2-receptor-mediated adenosine actions

Caffeine inhibition of sterigmatocystin, citrinin, and patulin production.

Abstract: , Microbiological medium was used to study the effect of caffeine on sterigmatocystin, citrinin, and patulin production by Aspergillus versicolor, Penicilliwn citrinum, and Penicillium urticae, respectively. Caffeine inhibited the growth of the three’ fungal species and de- creased sterigmatocystin and patulin production. The effect on citrinin production appeared to be limited to a delay in toxin synthesis. A preliminary examination of P. urticae suggested that caffeine’ s anti-mycotoxigenic activity does not involve a generalized inhibition of lipid synthesis. INTRODUCTION PREVIOUS INVESTIGATIONS have established that while cocoa and coffee beans are commonly contaminated with aspergilli (Hansen and Welty, 1970; Hiscocks, 1965), they are generally poor substrates for aflatoxin production (Levi et al., 1975; Nartowicz et al., 1979; Lenovich and Hurst, 1979; Llwewllyn et al., 1978). Nartowicz et al. (1979) and Lenovich (198 1) attributed this anti-aflatoxigenic activity to the caffeine content of these commodities. It has also been established that the addition of caffeine to micro- biological media at levels 21 mg/ml inhibits aflatoxin pro- duction (Buchanan and Fletcher, 1978), while theophyIline (Buchanan and Fletcher, 1978) and theobromine (Buchanan et al., 1978) have little activity. Similar results have been reported for ochratoxin A production by Aspergillus ochraceus (Buchanan et al., 1982). Buchanan et al. (1982) found that caffeine inhibited the growth of a number of mycotoxigenic Aspergillus and Penicillium species, and suggested that caffeine may have inhibitory activity against the production of a variety of polyketide mycotoxins. The objective of the present study was to characterize further caffeine’ s anti-myotoxigenic activity by determining its effect on the production of three additional polyketide mycotoxins; sterigmatocystin, citrinin, and patulin.

Developmental aspects of theophylline metabolism in premature infants

Abstract: The metabolic degradation of theophylline was studied in nine premature infants with postconception ages of 28 to 42 wk. Urinary and plasma metabolites (caffeine; theobromine; 3-methylxanthine; 1,3-dimethyluric acid; and 1-methyluric acid) and unchanged theophylline were analyzed with selected ion monitoring gas chromatography-mass spectrometry. The anticipated decrease in plasma caffeine (which is absent in adult human and children) did not occur in the postconception age range studied, but the urinary percentages of unchanged theophylline decreased from 61% at a postconception age of 28 to 32 wk to 43% at 38 to 42 wk. This suggests increasing theophylline metabolism with age due to developing hepatic cytochrome P-450 enzyme systems. The increased degradation of theophylline is largely explained by the production of 1,3-dimethyluric acid (from 20% to 34%). In infants of an older postconception age, theobromine, a caffeine metabolite, was also detected. To explain the difference of caffeine pathway between adults and premature infants, it is hypothesized that the caffeine pathway of theophylline is equally active in both age groups. The absence of caffeine metabolite in adults is due to the maturing caffeine-metabolizing enzymes, which degrade caffeine immediately to its metabolites.

Interaction between methylxanthines and the benzodiazepine receptor.

Abstract: 3H-Flunitrazepam (500 pM) was used to estimate the inhibitory effects of caffeine, theophylline, theobromine and 3-methylxanthine on binding to rat brain homogenates. Caffeine and theophylline showed a low affinity competitive type of inhibition in vitro, but no inhibition in vivo. Low concentrations of caffeine failed to show clear inhibitory capabilities against low concentrations of 3H-flunitrazepam. The results suggest that only the toxic central nervous system effects of methylxanthines are mediated via the benzodiazepine receptor.

HPLC Separation of Theophylline, Paraxanthine, Theobromine, Caffeine and Other Caffeine Metabolites in Biological Fluids

Abstract: An HPLC method is described for rapid analysis of caffeine and seven of its metabolites in plasma, urine, milk and saliva in a single operation using a 5 μ C18 reverse phase column. The metabolites are extracted with chloroform - iso-propanol (85:15) from 100 μL samples added to NH4HCO3. No interference from normal blood, urine, milk or saliva constituents was observed. The method is accurate and precise and separates 1,7-dimethylxanthine (paraxanthine) from 1,3-dimethylxanthine (theophylline). Sensitivity for most metabolites is in the range of 0.1 to 0.3 μg/mL and the detectability is at the nanogram level.

Concurrent measurement of theophylline and caffeine in neonates by an interference-free liquid-chromatographic method.

Abstract: A sensitive liquid-chromatographic method was developed for the simultaneous measurement of theophylline and caffeine within 6 min. The excellent resolution of the method allows the complete separation of theophylline, internal standard, and caffeine from frequently encountered interfering drugs including acetaminophen, acetazolamide, acetylsalicylate, ampicillin, 8-chlorotheophylline, cefazolin, cephalosporin C, cephalothin, cephapirin, chloramphenicol, dyphylline, metronidazole, 3-methylxanthine, salicylate, sulfadiazine, sulfamerizine, sulfamethazine, sulfamethoxazole, sulfisoxazole, and theobromine. The chromatographic system involves a Waters' Radial-Pak C18 reversed-phase column and acetonitrile in 0.1 mol/L potassium phosphate buffer, pH 4.0, (9.5/90.5 by vol) as the mobile phase. The method can detect theophylline or caffeine concentrations as low as 0.5 mg/L in 50 microL of serum. Precision and accuracy are excellent.

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.

Potentiating effects of methylxanthines on teratogenicity of mitomycin C in mice

Abstract: A previous study demonstrated that caffeine strongly potentiated the teratogenic action of mitomycin C in mice. In the present study the effect of methylxanthines including caffeine, theophylline, theobromine (theobromine sodium salicylate), paraxanthine, and 1-methylxanthine was compared in order to analyze the structure-activity relationship. Jcl:ICR mice were injected IP with 3 mg/kg of mitomycin C, immediately followed by SC injection of each methylxanthine on day 11 of gestation. The doses of methylxanthines were calculated so that the mice received 50 mg/kg of caffeine or the equimolecular amount of the other methylxanthines. Fetuses were examined for external malformations on day 18 of gestation. Mitomycin C at 3 mg/kg and the methylxanthines at the doses used were not teratogenic. Combined administration of caffeine or theophylline with mitomycin C produced more than 80% of malformed fetuses. Although less effective than caffeine or theophylline, paraxanthine also significantly increased the incidence of malformed fetuses. Theobromine and 1-methylxanthine were virtually ineffective. From these findings, it is suggested that the methyl group at N-1 position of the xanthines is important for the enhancement but the N-1 methylation alone is ineffective unless accompanied with the substitution of the methyl moiety at the other position(s).

Metabolic Relations between Methylxanthines and Methyluric

Abstract: Metabolism of purine alkaloids in the leaves of Coffea dewevrei De Wild et Durand var excelsa Chev, Coffea liberica Bull ex Hiern and Coffea abeokutae Cramer was studied by analyzing leaf discs collected during vegetative development and by feeding the following radioactive tracers: ['4Cjtheobromine, I'4Clcaffeine, and I'4Cjtheacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites were quantitatively and qualitatively determined. All three species convert the precursors to the same radioactive products, and proceed through the same four maturity stages characterized by the alkaloid accumulation pattern and by a particular transformation potency: (stage 1) young plant accumulating caffeine, transforms theobromine to caffeine; (stage 2) caffeine is gradually replaced by theacrine, theobromine and caffeine are converted to theacrine; (stage 3) theacrine disappears whereas liberine (0(2), 1,9thrimethyluric acid) accumulates, theacrine is metabolized to liberine; (stage 4) branched-out plant containing liberine but no theacrine, caffeine is converted rapidly to liberine via theacrine. Methylliberine (0(2),1,7,9tetramethyluric acid), presumably the direct precursor of liberine, is occasionally found in low concentrations at stage 3 and 4. The collective term 'liberio-excelsoid' introduced by geneticists for the numerous races or species of Pachycoffea is in accordance with the phytochemical equality found in this work.

Determination of Purine Bases in Formulations and Natural Products

Abstract: A selective GLC procedure for the determination of caffeine, theophylline and theobromine is presented. Theophylline and theobromine were methylated with Methelute and determined as caffeine. The GLC procedure proved to be simpler and more time saving than the spectrophotometric methods without loss of accuracy. The interference of accompanying ingredients could be, eliminated.

A contribution to the chemistry of sterculia diversifolia donn cultivated in egypt

Abstract: From Sterculia diversifolia Donn, luteolin, quercetin, kaempferol, quercetin-3- arabinoside and P-Coumaric and isochlorogenic acide were isolated from the leaves. While, caffeine, theobromine, theophylline and choline were isolated from the defatted seeds. Lipids of all the organs showed the presence of a hydrocarbon m.p. 58°C, a-amyrin and b-Sitosterol in the unsaponifiable fraction. Fatty acids were found to be oleic, myristis, palmitic and stearic.

Theophylline therapy: the need for pharmacy involvement

Abstract: Methylxanthines (theophylline, caffeine, theobromine) have been utilized in the treatment of asthma for nearly 50 years. For many years, it was thought that the pharmacological mechanism of action was inhibiting phosphodiesterase. Now, other basic cellular actions of the methylxanthines have received major attention in studies to explain their diverse effects. Listed in order of their increasing sensitivity to methylzanthines, they are: (1) those associated with the translocations of intracellular calcium; (2) those mediated by increasing accumulation of cyclic nucleotides, particularly cyclic-AMP; (3) those mediated by blockage of receptors for adenosine (Gilman et al., 1980). Because the concentration of free theophylline in plasma rarely exceeds 50 μmol during therapy, this fact alone appears to limit severely the possible contribution of the other categories of action and leaves the blockage of receptors for adenosine as the leading candidate (Gilman et al., 1980).

Bromo- and iododemercuration of 8-trifluoroacetoxymercuri derivatives of theophylline and theobromine

Abstract: Direct C-mercuration in the 8 position of N-acyl derivatives of theophylline and theobromine with mercury(II) trifluoroacetate in a mixture of anhydrous trifluoroacetic acid and trifluoroacetic anhydride is described. 8-Bromo and, respectively, 8-iodo derivatives of both dimethylxanthines were obtained in high yields from 8-trifluoroacetoxymercuri derivatives by the action of an aqueous solution of potassium tribromide or a solution of iodine in acetonitrile.