Xanthine theophylline

Of the xanthines, theophylline is the most effective bronchodilator, and it has been shown repeatedly both to relieve airflow obstruction in acute asthma and to reduce the severity of symptoms and time lost from work or school in patients with chronic asthma. Theophylline base is only slightly soluble in water, so it has been administered as several salts containing varying amounts of theophylline base. Most preparations are well absorbed from the gastrointestinal tract, but absorption of rectal suppositories is unreliable. 

Caffeine (40 R1 = R2 = R3 = Me) is a powerful CNS stimulant, and the other xanthines theophylline and theobromine have rather less activity. The popularity of beverages containing xanthines depends on this stimulant effect. Caffeine is useful in morphine poisoning. 

Q10 Other bronchodilator agents include nebulized ipratropium. Ipratropium is a muscarinic receptor antagonist that helps to relax bronchial smooth muscle which has contracted via parasympathetic stimulation. The xanthines theophylline and aminophylline (theophylline ethylenediamine) are alternative bronchodilator agents. These agents may act as phosphodiesterase inhibitors and, although they have been used as bronchodilators for many years, adverse CNS, GI and cardiovascular effects may limit their usefulness. 

Theophylline. The prototypic xanthine, theophylline.h known to promote a weak diuresis by. stimulation of cardiac function and by a direct action on the nephrtrn. Although ii is infircquently used as a diuretic, diuresis may be an ub-served side effect when it is used as a bronchodilator. 

Figure 3. Van t Hoff plots showing the effect of temperature on the equilibrium association constants, K, of both xanthines ( theophylline 1,3-dipropylxanthine x 1,3-dibutylxanthine) and xanthine-7-ribosides ( theophylline-7-riboside O 1,3-dipropyl-xanthine-7-riboside a 1,3-dibutylxanthine-7-riboside). All plots were essentially linear (r > 0.95). Reproduced with permission of principal author and publisher of ref. [34].

The xanthine theophylline has been used for several decades in the treatment of asthma. This compound produces different effects at the cellular level, including phosphodiesterase isoenzyme inhibition, adenosine antagonism, catecholamine secretion enhancement, and the modulation of calcium fluxes. Recently, theophylline was found to have both immunomodulatory and anti-inflammatory properties therefore, interest in its use in patients with asthma has been renewed [103]. Recent studies have thus discovered that at low doses, theophylline is able to decrease airway inflammation, accelerate eosinophil apoptosis, and decrease recruitment of lymphocytes and neutrophils to the lungs. Although it is classified as a phosphodiesterase inhibitor, its exact therapeutic mechanism of action remains undetermined [104]. Of the new mechanisms that have been included in the potential mode of action of theophylline, one is the apoptosis of inflammatory cells. In eosinophils and lymphocytes, for example, this effect is due to the compound s ability to inhibit phosphodiesterase, which leads to an even more pronounced increase in intracellular cAMP levels than that which occurs when adenylate cyclase, the enzyme that synthesizes cAMP, is activated. This inhibition and the resulting cAMP level increase thus lead to... 

The natural products theophylline 34 (1,3-dimethylxanthine), theobromine 35 (3,7-dimethylxanthine) and caffeine 36 (1,3,7-trimethylxanthine) are derived from the lactam form of xanthine. Theophylline occurs in tea leaves and is a diuretic and a coronary vasodilator. Cocoa beans contain ca. 5% theobromine, which is a stronger diuretic than theophylline or caffeine. 

Caffeine, mp 263°C, sublimes on heating and is more soluble than dimethylxanthines. Caffeine has a stimulating effect on the central nervous system. It is extracted from green coffee beans with liquid CO2 [151]. Caffeine is synthesized by methylation of xanthine, theophylline or theobromine with methyl iodide or dimethyl sulphate [149]. 

Maxwell DL, Fuller RW, Conradson T-B, Dixon CMS, Aber V, Hughes JMB, Barnes PJ. Contrasting effects of two xanthines, theophylline and enprofylline, on the cardio-respiratory stimulation of infused adenosine in man. Acta Pl siol Scand( 9S1) 131,459-65. 

In 1895, Emil Fischer (1852-1919) published what was supposedly the first synthesis of caffeine. [515, 516] However, this was not the case, because the assumed structures of xanthine, theophylline [517] and caffeine were in fact wrong. He had believed, that they were 2,8-dioxopurines. 

Figures Chromatograms on MIL-53(Al)-packed column (7-cm longx4.6-mm i.d.) for RP HPLC separation using CHjCN/HjO as mobile phase at l.OmLmin b (a) ethylbenzene and toluene (b) PAHs (c) thiourea (1), phenol (2), aniline (3), benzaldehyde (4), bromobenzene (5), naphthalene (6) (d) o-benzenediol, m-benzenediol, and p-benzenediol (e) aniline, N,N-dimethylaniline, and m-nitroaniline (f) xanthine, theophylline, and caffeine. Mobile phase composition (CHjCN/HjO, v/v) (a) 7 3 (b) 10 0 (c) 6 4 (d) 1 9 (e) 9 1 (f) 5 5. UV detection at 210 run (a, c), 256 run (b), 70 run (f), and 280 nm (d, e). (Reproduced from Ref 69 with permission of The Royal Society of Chemistry. DOI 10.1039/C2AN15925B.)...

Based upon these results, a simple, rapid, reproducible and accurate voltammetric method was proposed for the determination of xanthine, theophylline, theobromine and caffeine in the micromolar concentration range [26], The analytical performance characteristics of the method are comparable to those reported for the determination of xanthines by the use of chemically modified electrodes, biosensing techniques and differential pulse voltammetry. The excellent results obtained for caffeine determination in commercially available products, with very simple sample preparation, involving only dilution in electrolyte, demonstrates the practical analytical utility of the method. 

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