Theophylline, in tea

This experiment describes a quantitative analysis for caffeine, theobromine, and theophylline in tea, pain killers, and cocoa. Separations are accomplished by MEKC using a pH 8.25 borate-phosphate buffer with added SDS. A UV detector set to 214 nm is used to record the electropherogram. An internal standard of phenobarbital is included for quantitative work. 

Nishizawa, M., Chonan, T., Sekijo, L, and Sugii, T. 1982. Quantitative determination of caffeine, theobromine, and theophylline in tea, coffee, and cocoa by high-performance liquid chromatography. Hokkaidoritsu Eisei Kenkyushoho 32 7-11. 

Beyond Viagra, there are a number of other PDE inhibitors that are used clinically. In fact, the classic drugs papaverine and dipyridamole were used clinically before their effects on PDEs were known. Caffeine and theophylline (a compound found in tea) are also PDE inhibitors. However, all of these drugs most likely have multiple targets, making conclusions regarding the roles of PDEs in processes that are sensitive to these agents difficult to interpret. Certainly, some of their effects are due to their actions on adenosine receptors. 

Several studies have investigated the biosynthesis of caffeine in tea. The results of a study by Suzuki and Takahashi27 30 suggest a pathway for caffeine biosynthesis in tea from 7-methylxanthine to theobromine and then to caffeine. Additionally they suggest that theophylline is synthesized from 1-methylxanthine. Another study by Ogutuga and Northcote31 proposes a pathway through 7-methylxanthosine to theobromine followed by caffeine. 

There are numerous methods in the literature for the determination of caffeine, theobromine, and theophylline in food matrices, including coffee, tea, and cocoa. Until recently, methods have emphasized the determination of the major methylxanthines in a commodity, for example, caffeine in coffee or theobromine in cocoa. Present methods range from being specific for one of the compounds in a single matrix to being an all-encompassing assay of major and minor methylxanthines in food products. 

HPLC allows a quantitative determination with relatively simple extractions. In many cases, extraction only involves a heating of the commodity with water, followed by filtration and injection onto an HPLC column. In the determination of caffeine, theobromine, and theophylline in cocoa, coffee, or tea, as well as in other foods, there is scarcely a month that passes without a new paper on this assay. Kreiser and Martin provide typical conditions for analysis.28 In their studies, samples were extracted in boiling water and filtered prior to injection onto the HPLC column. The HPLC conditions used a Bondapak reversed phase column and a mobile phase of water methanol acetic acid (74 25 1) with detection at 280 nm. This method is accurate, precise, and conserves time. It has also been adopted by the AOAC as an official method for the determination of theobromine and caffeine in cocoa beans and chocolate products.29... 

Theophylline levels in tea are less than 0.04% on a dry-weight leaf basis. Little is known about the causes of variation in experimental reports, and may be attributed to experimental error or degradation of caffeine as a result of experimental procedure. One report did not detect theophylline in a variety of commercially available tea extractions.32... 

There is also confusion in the literature concerning theobromine and theophylline levels in tea beverage. The most reliable data indicate 0.16 to... 

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. 

Caffeine in tea and coffee inhibits the phosphodiesterase that degrades cAMP. The resultant increase in cAMP levels, therefore, mimics the action of mediators such as the catecholamines that modulate adenylate cyclase. Caffeine and the related theophylline (both purine alkaloids, see Box 11.12) are thus effective stimulants of the CNS. 

A plant-derived compound used in the treatment of asthma and COPD is the methylxanthine-type alkaloid, theophylline (50), found naturally in tea Camellia sinensis Kuntze). This compound demonstrated higher activity when complexed with bases, as in its semisynthetic analogue amino-phylline (51). 5... 

A variety of xanthines including caffeine, theobromine, and theophylline have been found from food materials including.coffee, chocolate, and tea (419-420). Theophylline determination in sera has been much studied. The technique allows the determination of theophylline at serum levels of 1.5-20 mg/liter theophylline with sample sizes ranging from 50 to 10 /xl (42 -425). Hill (426) assayed theophylline using 50 /xl of serum and an analysis time of 8 min with good interbatch precision and accuracy. Alternative methods which allow the determination of as little as 0.1 mg/ml (427) or 20 ng theophylline in 10 ml serum have been described (428). 

Several purine derivatives are found in nature, e.g. xanthine, hypoxanthine and uric acid. The pharmacologically important (CNS-stimulant) xanthine alkaloids, e.g. caffeine, theobromine and theophylline, are found in tea leaves, coffee beans and coco. The actual biosynthesis of purines involves construction of a pyrimidine ring onto a pre-formed imidazole system. 

The xanthines caffeine (40 R1 = R2 = R3 = Me), theophylline (40 R1 = R2 = Me, R3 = H) and theobromine (40 R1 = R3 = Me, R2 = H), which are the stimulants present in tea, coffee, cocoa and many other beverages, have a number of therapeutic uses. They were formerly used as diuretics, theophylline being the most potent, and caffeine is a powerful CNS stimulant useful in treating cases of poisoning by CNS depressants. Caffeine has also been... 

Theophylline is found in coffee and in tea in very small amounts, but it has a stronger effect on the heart and breathing than does CF. Along with CF, TP is used as a medicine to treat emphysema and bronchitis (254,255). Caffeine and TP inhibit cAMP phosphodiesterase. In their presence the effects of cAMP, and thus the stimulatory effects of the hormones that lead to its production, are prolonged and intensified. 

This neurotransmitter has diverse functions throughout the brain that are also related to our sleep—wake cycles. We know a lot about it because of the ready availability of a very safe, highly effective adenosine receptor antagonist that is served hot or cold, with or without cream, throughout the world—caffeinated coffee Caffeine is also commonly found with theophylline (a molecule that is very similar to caffeine) in tea. Indeed, although caffeine is found in at least 63 plant species, 54% of the world s... 

Caffeine, the active substance responsible for the stimulant effect of the coffee plant s berry, is a methyl-xanthine, one of the family of stimulants present in more than 60 species of plants. The pure chemical forms white, bitter-tasting crystals, which were first isolated from coffee in 1820. Other family members are theophylline, found in tea leaves, and theobromine, found in the cacao pods that are ground to make chocolate. The most potent component in the coffee family by unit weight is theophylline, while theobromine, the weakest component by unit weight, stays in the body longer than does caffeine. 

Breathing rate increases in response to caffeine. The effect on respiration occurs at the level of the brain stem s respiration control center. Theophylline has the most potent action of all the methylxanthines, affecting the smooth muscle of the bronchial tree in the lungs. This is why theophylline is a treatment for asthma. Doctors may recommend weak tea for their asthmatic patients with colds this bronchodilating action of the theophylline in the tea will aid in clearing mucus. 

The major bases found in nucleic acids are adenine and guanine (purines) and uracil, cytosine, and thymine (pyrimidines). Thymine is found primarily in DNA, uracil in RNA, and the others in both DNA and RNA. Their structures, along with their chemical parent compounds, purine and pyrimidine, are shown in Figure 10.1, which also indicates other biologically important purines that are not components of nucleic acids. Hypoxanthine, orotic acid, and xanthine are biosynthetic and/or degradation intermediates of purine and pyrimidine bases, whereas xanthine derivatives—caffeine, theophylline, and theobromine—are alkaloids from plant sources. Caffeine is a component of coffee beans and tea, and its effects on metabolism are mentioned in Chapter 16. Theophylline is found in tea and is used therapeutically in asthma, because it is a smooth muscle relaxant. Theobromine is found in chocolate. It is a diuretic, heart stimulant, and vasodilator. 

Methylxanthines include theophylline [thee OFF i lin] found in tea, theobromine [thee o BRO min] found in cocoa, and caffeine [kaf EEN]. Caffeine, the most widely consumed stimulant in the world, is found in highest concentration in coffee but is also present in tea, cola drinks, chocolate candy, and cocoa. 

The alkaloids are basic compounds in which an N atom is typically part of a heterocyclic ring but in some cases is merely a substituent of an alicyclic or aromatic ring system (as for example with colchicine, some peptide alkaloids and some Amaryllidaceae alkaloids). Various N-based heterocyclics such as the purine and pyrimidine bases of DNA and RNA (see Chapter 2) and the methylxanthine purine derivatives variously found in tea and coffee (caffeine, theobromine and theophylline) are sometimes referred to as pseudoalkaloids and for consistency will be included as alkaloids in this classification. Indeed all plant heterocyclics with a ring N will be conveniendy lumped in with the alkaloids in the tables for didactic simplicity and consistency. 

Methylxanthine is the major purine constituent of human urine (3.1 g in 10001) (1898ZPC(24)364). 3- and 7-Methylpurines are also minor constituents of urine, especially following large doses of caffeine or other methylated xanthines. 1,3-Dimethylxanthine (theophylline) occurs with caffeine in tea leaves and is a powerful diuretic and has been used clinically for this purpose (generally as an adduct with salts of organic acids) and also in the treatment of asthma. 1,7-Dimethylxanthine (paraxanthine) is also an efficient diuretic and, in addition, possesses antithyroid properties (45JCS751). The main purine constituent... 

The alkaloid caffeine is found in coffeef tea, and kola. It is also known less commonly by the name of theine, especially as found in tea. The amount present in coffee and tea is from 1-4.8 per cent in tea and 1-1.5 per cent in coffee. Caffeine crystallizes from water or alcohol, m.p. 234°. It is slightly soluble in water, less so in alcohol and ether and more in chloroform. It acts as a weak base. It may be prepared from either theobromine or from theophylline by further methylation, which confirms the constitution as the 1-3-7-tri-methyl product. 

The two alkaloids theobromine and theophylline are isomeric, theobromine being the 3-7-di-methyl xanthine and theophylline the I-3-di-methyl xanthine. Theobromine is the principal alkaloid of the cocoa bean. Cacao theohroma. It occurs also in small amounts in kola nuts and tea leaves. Theophylline is present in small amounts in tea. They both resemble caffeine in being crystalline, weak bases. 

Methylxanthines, especially theophylline, in healthy subjects inhibit solute reabsorption in both the proximal nephron and the diluting segment without changing either glomerular filtration rate or renal blood flow appreciably. Accordingly, an apparent increase in creatinine clearance in a heavy tea drinker has been attributed to a discrepancy between GFR and creatinine clearance (22). 

Cafleine, theobromine and theophylline, and related methylxanthine compounds, are mild stimulants and have everyday use, e.g. in tea. coffee, chocolate and some soft drinks. Methylxanthines work in part as PHOSPHODIESTERASE INHIBITORS and in part as antagonists at P,-purinoceptors (see ADENOSINE RECEPTOR ANTAGONISTS). 

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