Theophylline, coffee

The main sources of these compounds are tea, cocoa, and coffee. Theophylline has the highest interest as a broncholytic. 

Caffeine (coffee) Theophylline (tea) Theobromine (cocoa) Caffeine... 

Caffeine. About 3% by weight of the roasted coffee bean is caffeine (16). The second U.S. Department of Agriculture world coffee crop estimate for 1988—1989 was 4.24 x 10 kg (93.3 million 100-lb bags) (102). World coffee consumption was predicted to rise in the foreseeable future at the rate of 1—2% per year and thus the total amount of caffeine and related alkaloids ingested from this source can also be expected to increase. Caffeine and related bases (eg, theophylline) are also found in various teas but, because most of the major producers (India, China, etc) export relatively Htfle of thek crops and keep most for domestic consumption, accurate figures on year-to-year production are more difficult to obtain. Nevertheless, these crops are of significant economic import (103). 

For many years oral xanthines, shown in Table 2, were the preferred first-line treatment for asthma in the United States, and if the aerosol and oral formulations of P2" go sts are considered separately, as they are in Table 1, this was still the case in 1989. Within this class of compounds theophylline (8), or one of its various salt forms, such as aminophylline [317-34-0] (theophylline ethylenediamine 2 l), have been the predominant agents. Theophylline, 1,3-dimethylxanthine [58-55-9], is but one member of a class of naturally occurring alkaloids. Two more common alkaloids are theobromine (9), isomeric with theophylline and the principal alkaloid in cacao beans, and caffeine, (10), 1,3,7-Trimethylxanthine [58-08-2], found in coffee and tea. 

Methybcanthine Diuretics. The mild diuretic effect of drinking coffee, from caffeine, and tea, mainly from theophylline, has been recogni2ed for along time. But the methylxanthines (Table 5) are of very limited efficacy when used as diuretics. The excretion of sodium and chloride ions are increased, but the potassium excretion is normal. Methylxanthines do not alter the urinary pH. Even though the methylxanthines have been demonstrated to have minor direct effects in the renal tubules, it is beUeved that they exert their diuretic effects through increased renal blood flow and GER (71). 

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. 

Caffeine was conceived for a wide range of readers interested in the effects on human health, nutrition, and physiological function of the methylxanthine beverages and foods—tea, coffee, mate, cola beverages, and cocoa and chocolate products. These products supply one or more of the dietary methylxanthines—caffeine, theobromine and theophylline— and are an integral part of the diet of many people in many countries. The interest in the health effects of both the methylxanthines in isolation and in the products containing them has grown rapidly in recent years. 

The methylxanthines of interest are caffeine (1,3,7-trimethylxanthine), theophylline (1,3-dimethylxanthine), and theobromine (3,7-dimethylxanthine) and they occur in coffee, tea, mate, cocoa products, and cola beverages. This chapter is an introduction to their chemistry, isolation, and biosynthesis. While the class of methylxanthines is large and comprised of more members than these three, this chapter will essentially be limited to caffeine, theobromine, and theophylline. 

The analysis of the methylxanthines (caffeine, theobromine, and theophylline) is important in the areas of nutrition and clinical chemistry. These three compounds compose the majority of the alkaloids present in coffee, tea, cocoa, cola nuts, and guarana. 

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... 

Theobromine and theophylline concentrations are relatively low in coffee the values in green coffee beans are, respectively, 20 and 5 mg/kg.3... 

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. 

Liver metabolism is affected by methylxanthines. In high doses, theophylline and caffeine increase the level of cyclic AMP. Very high levels of methylxanthines decrease the level of branched chain and aromatic amino acids in plasma. Coffee appears to have little effect on ethanol metabolism. 

Alkaloids are compounds that contain nitrogen in a heterocyclic ring and are commonly found in about 15-20% of all vascular plants. Alkaloids are subclassified on the basis of the chemical type of their nitrogen-containing ring. They are formed as secondary metabolites from amino acids and usually present a bitter taste accompanied by toxicity that should help to repel insects and herbivores. Alkaloids are found in seeds, leaves, and roots of plants such as coffee beans, guarana seeds, cocoa beans, mate tea leaves, peppermint leaves, coca leaves, and many other plant sources. The most common alkaloids are caffeine, theophylline, nicotine, codeine, and indole... 

After the nucleic acid purines adenine and guanine, the next most prominent purine in our everyday lives is probably caffeine. Caffeine, in the form of beverages such as tea, coffee, and cola, is one of the most widely consumed and socially accepted natural stimulants. Closely related structurally are theobromine and theophylline. Theobromine is a major constituent of cocoa, and related chocolate products. Caffeine is also used medicinally,... 

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 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). 

Many antibiotics produced by various microorganisms are nucleosides (2). Among these are nebularine, cordycepin, and nucleocidin. The only known purines in higher plants shown to be involved In allelopathy are caffeine, theophylline, paraxanthine, and theobromine from the coffee tree... 

The Coffee (syn. Madder) botanical family (Rubiaceae Juss.) (Table 15) consists of more than 400 genera and over 6000 species. It grows in the tropics and the sub-tropics. Plants belonging to this family include trees, bushes and liane. The Coffee plant family contains two major purines of adenine- /guanine-derived alkaloids, the so-called purine alkaloids . Purine is a nitrogenous base of nucleotide, which consists of just purine and pentose sugar (o-ribose or 2 deoxy-D-ribose). Typical purine alkaloids are caffeine, theophylline and theobromine. The same or similar purine alkaloids occur also in other plant families. 

Methyixanthines include caffeine (present in coffee and tea), theobromine (tea and chocolate), and theophylline (tea). 

Three xanthines are pharmacologically important caffeine, theophylline, and theobromine. All three alkaloids, which occur naturally in certain plants, are widely consumed in the form of beverages (infusions or decoctions) derived from these plants. Coffee primarily contains caffeine (about 100-150 mg per average cup) tea contains caffeine (30-40 mg per cup) and theophylline and cocoa contains caffeine (15-18 mg per cup) and theobromine. Cola drinks also contain significant amounts of caffeine (about 40 mg/12 oz). The CNS stimulation associated with these beverages is predominantly due to the caffeine. 

A variety of drugs in distinct pharmacological and chemical classes can be considered under the broad classification as stimulants. Xanthines and methylxan-thines constitute a weak class of stimulants that includes caffeine, theophylline (aminophylline),and theobromine. Caffeine is freely available in coffee, colas, and certain over-the-counter pills. A low degree of tolerance develops to some of their effects and a mild withdrawal syndrome is observed following immediate cessation of their repeated use. 

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 three important methylxanthines are theophylline, theobromine, and caffeine. Their major source is beverages (tea, cocoa, and coffee, respectively). The importance of theophylline as a therapeutic agent in the treatment of asthma has waned as the greater effectiveness of inhaled adrenoceptor agents for acute asthma and of inhaled anti-inflammatory agents for chronic asthma has been established, but theophylline s very low cost is an important advantage for economically disadvantaged patients in societies in which health care resources are limited. 

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