Theophylline activity

Daly, JW, Airalogs of caffeine and theophylline activity as antagonists at adenosine recept< s. In Role of adenosine and adenine nucleotides in the biological system, (eds. Imai, S, Nakazawa, M), Elsevier science BV, Amsterdam, 1991,119-129. 

This experiment describes the quantitative analysis of the asthma medication Quadrinal for the active ingredients theophylline, salicylic acid, phenobarbital, ephedrine HGl, and potassium iodide. Separations are carried out using a Gi8 column with a mobile phase of 19% v/v acetonitrile, 80% v/v water, and 1% acetic acid. A small amount of triethylamine (0.03% v/v) is included to ensure the elution of ephedrine HGl. A UV detector set to 254 nm is used to record the chromatogram. 

C. G. A. Persson, Agents and Actions (Suppl.) 13, 115 (1983). A review on Theophylline stmcture-activity relationships. 

Pentoxifylline is stmcturaHy related to other methylxanthine derivatives such as caffeine [58-02-2] (1,3,7-trimethylxanthine), theobromine [83-67-0] (3,7-dimethylxanthine), and theophylline [58-55-9] (3,7-dihydro-1,3-dimethyl-1 H-piirine-2,6-dione or 1,3-dimethylxanthine), which also show radioprotective activity in some instances, suggesting that methylxanthines as a dmg class may radioprotect through a common mechanism (see Alkaloids). In a retrospective analysis of cervical and endometrial cancer patients receiving primary or adjuvant XRT, no association between caffeine consumption and incidence of acute radiation effects has been found. However, there was a decreased incidence of severe late radiation injury in cervical cancer patients who consumed higher levels of caffeine at the time of thek XRT (121). The observed lack of correlation between caffeine consumption and acute radiation effects is consistent with laboratory investigations using pentoxifylline. 

Xanthines such as caffeine (1)> theophylline (aminophylline) (2), and theobromine (3) are a class of alkaloids that occur in numerous plants. The CNS stimulant activity of aqueous infusions containing these compounds has been recognized since antiquity. This has, of course, led to widespread consumption of such well-known beverages as coffee (Coffea arabica), tea (Thea sinesis), mate, and cola beverages (in part Cola acuminata). The annual consumption of caffeine in the United States alone has been estimated to be in excess of a billion kilos. The pure compounds have found some use in the clinic as CNS stimulants. In addition, caffeine is widely used in conjunction with aspirin in various headache remedies. 

A derivative of an isomeric azapurine ring system interestingly exhibits bronchodilator activity, possibly indicating interaction with a target for theophylline. The starting pyridazine 97 is available from dichloro compound 96 by sequential replacement of the halogens. Treatment of 97 with formic acid supplies the missing carbon and cyclizes the intermediate formamide with consequent formation of zindotrine (98) [16]. 

Use of the macrolides increases serum levels of digoxin and increases the effects of anticoagulants. Use of antacids decreases the absorption of most macrolides. The macrolides should not be administered with clindamycin, lincomycin, or chloramphenicol a decrease in the therapeutic activity of the macrolides can occur. Concurrent administration of the macrolides with theophylline may increase serum theophylline levels. 

When Hie cholinesterase inhibitors are administered with the anticholinergic drugp, there is a potential decrease in activity of the anticholinergic drug. There is an increased risk of toxicity of theophylline when the cholinesterase inhibitors are administered with tacrine There is a synergistic effect when tacrine is administered with succinyl-choline, cholinesterase inhibitors, or cholinergic agonists (eg, bethanechol). 

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

A number of studies have shown that adenosine inhibits neuronal firing both in vitro and in vivo and is itself released during intense neuronal activity. It can protect against PTZ seizures in rodents while the antagonist theophylline is proconvulsant. No clear picture of its role in human epilepsy has emerged. 

May affect activity theophylline adjusted to a serum Cromolyn (nebulizer is preferred or MDI with... 

Theophylline is not recommended for treatment of acute asthma.2 It provides no additional benefit when optimal inhaled bronchodilators are used and increases the risk of adverse events. Similarly, although magnesium has bron-chodilator activity, it offers no significant benefits when optimal bronchodilator therapy is used.12,40... 

Foods derived from cocoa beans have been consumed by humans since at least 460 to 480 AD. The source of cocoa beans, the species Theobroma, contains a variety of biologically active components. These include the purine alkaloids theobromine, caffeine, and theophylline. Structurally, they are methylated xanthines and, thus, are often referred to as methylxanthines. Theobromine (3, 7-dimethylxanthine) is the predominant purine alkaloid in cocoa and chocolate. Caffeine (1, 3, 7-trimethylxanthine), the major purine alkaloid found in coffee and tea, is found in cocoa and chocolate at about one eighth the concentration of theobromine. Only trace amounts of theophylline (1, 3-dimethylxanthine) are detected in cocoa and chocolate products. 

Kuhne T., Homstein A., Semple J., et al. Flow cytometric evaluation of platelet activation in blood collected into EDTA vs. Diatube-H, a sodium citrate solution supplemented with theophylline, adenosine and dipyridamole. Am J Hematol 1995 50,40-5. 

Theophylline appears to produce bronchodilation by inhibiting phosphodiesterases, which may also result in antiinflammatory and other nonbronchodilator activity through decreased mast cell mediator release, decreased eosinophil basic protein release, decreased T-lymphocyte proliferation, decreased T-cell cytokine release, and decreased plasma exudation. 

Several derivatives of imidazo[2,l-/]theophyllines were synthesized and tested for their CNS activity. Compounds 476 showed significant antiserotonin and long-lasting hypothermic effects, and both 477 and 478 possess anticonvulsant properties <1999EJM1085, 2002FA697>. 

In a further application of MI-SPE, theophylline could be separated from the structurally related caffeine by combining the specific extraction with pulsed elution, resulting in sharp baseline-separated peaks, which on the other hand was not possible when a theophylline imprinted polymer was used as stationary phase for HPLC. A detection limit of 120 ng mb1 was obtained, corresponding to a mass detection limit of only 2.4 ng [45]. This combination of techniques was also used for the determination of nicotine in tobacco. Nicotine is the main alkaloid in tobacco and is the focus of intensive HPLC or GC analyses due to its health risk to active and passive consumers. However, HPLC- and GC-techniques are time-consuming as well as expensive, due to the necessary pre-purification steps required because the sample matrices typically contain many other organic compounds besides nicotine. However, a simple pre-concentration step based on MI-SPE did allow faster determination of nicotine in tobacco samples. Mullett et al. obtained a detection limit of 1.8 jig ml 1 and a mass detection limit of 8.45 ng [95]. All these examples demonstrate the high potential of MI-SPE to become a broadly applicable sample pre-purification tool. 

Devries MH, Rademaker CM, Geerlings C, Vandijk A and Noordhoek J (1989) Pharmacokinetic Modeling of the Effect of Activated-Charcoal on the Intestinal Secretion of Theophylline, Using the Isolated Vascularly Perfused Rat Small-Intestine. J Pharm Pharmacol 41 pp 528-533. 

Caffeine pharmacokinetics are nonlinear. For example, when comparing a 500 mg dose to a 250 mg dose, the clearance is reduced and elimination half-life is prolonged with the higher dose (Kaplan et al. 1997). Thus, larger doses prolong the action of the drug. Active metabolites of caffeine are paraxanthine, and to a lesser degree, theobromine, and theophylline. Urinary metabolites are I-methylxanthine, l-methyluric acid, and an acetylated uracil derivative. 

Theophylline (Fig. 20) is structurally very similar to caffeine and present at a low concentration in tea. It is also known as dimethyl xanthine. It is used for the treatments of asthma and COPD, for more than 50 years despite its many side effects. The mechanism of beneficial effect of theophylline is through HD AC activation. 

Failla M, To Y, Ito M, Adcock IM, Barnes PJ, Ito K. (2007) Oxidative stress-induced PI3-kinase activation reduces HDAC activity and is inhibited by theophylline. Proc Am Thorac Soc 2 A45 (Abstr.)... 

---