Central nervous system stimulants theobromine

Caffeine and theophylline are more active on the central nervous system, while theobromine is much less active. Caffeine and theophylline also appear to stimulate the respiratory centers, making them useful in the treatment of infants who stop breathing for extended periods of time (sleep apnea), which can lead to sudden infant death. 

Other constraints are important for more complex products, for which mass is not central, but value. For example, central nervous system stimulants are a new class of substances addressed by production with engineered baker s yeast. Expressing the biosynthetic pathways for the opioids thebaine and hydrocodone, and parts of the morphine pathway in yeast, a first step is taken for easy production of opiates [21, 22]. This opens the possibility for the development of new painldllers with less addictive potential. However, it clearly is a new technology that could be abused with many negative consequences - so some contemplation about how to control these developments seems advisable [23]. Not only are narcotics in the center of interest but stimulants such as caffeine and theobromine have also recently been produced with genetically engineered 5. cerevisiae strains [24]. 

Caffeine is the most widely consumed central-nervous-system stimulant. It also relaxes smooth muscles, stimulates the cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Moreover, it has potent antioxidant properties, helps in protecting cells against the UV radiation, and slows down the process of photo-aging of the skin [250]. Theobromine is used as a bronchodilator, as a vasodilator, as a diuretic, and in the treatment of angina pectoris and hypertension [251]. 

AH three of these materials are apparentiy central nervous system (CNS) stimulants. It is beheved that for most individuals caffeine causes greater stimulation than does theophylline. Theobromine apparentiy causes the least stimulation. There is some evidence that caffeine acts on the cortex and reduces drowsiness and fatigue, although habituation can reduce these effects. 

The generic name of the cacao tree (Theobroma) means food of the Gods and gives its name to a caffeine-like stimulant, theobromine (a methylxanthine). It has been claimed that the theobromine in chocolate is responsible for its addictive characteristics. This is based on the fact that methylxanthines bind to adenosine receptors in the central nervous system and act as antagonists to this neurotransmitter (Chapter 14). However, another group of substances, the amides formed between ethanolamine and unsaturated fatty acids, are also possible candidates for the title of the chocolate drug . 

These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see Box 14.3) and subsequent release of adrenaline. This leads to the major effects a stimulation of the central nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

Thea assamica Mast T. bohea L. T. cantoniensis Lour. T. chinensis Sims. T. cochinchinensis Lour. T. sinensis L. T. viridis Link. Cha (Tea) (leaf) Caffeine, theophylline, tannic acid, theobromine, xanthine, polyphenols. 33-47.405,406,409 Diuretic effect, increase renal blood flow, stimulate central nervous system, antitumor, prevent lung cancer. 

Camellia sinensis (L.) Kuntze China Caffeine, theophylline, tannic acid, theobromine, xanthine.33,47 Diuretic effect, increases renal blood flow, stimulate central nervous system. 

These all resemble each other in most points of their pharmacological action, but they differ markedly in the relative intensity of their action on various functions. Thus, caffeine is the most potent central nervous system (CNS) stimulant of the group theobromine exerts the greatest action on the muscles and theophylline is the most effective diuretic and coronary dilator. Theobromine has comparatively little effect on the CNS, whereas theophylline has no action on the muscles. 

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]. 

Xanthine derivatives have a number of pharmacological properties in common. Five major actions are observed (1) central nervous system and respiratory stimulation, (2) skeletal muscle stimulation, (3) diuresis, (4) cardiac stimulation, and (5) smooth-muscle relaxation. Caffeine (29) increases central nervous system activity and its main effect is on the cerebral cortex, where it acts to produce clear thought and reduce drowsiness and fatigue. The normal dose is 100-200 mg (Cordell, 1981). The oral LD50 in mouse is 127-137 mg/kg the oral LD50 in rat for theobromine (31) is 950... 

The phosphodiesterase which cleaves cyclic AMP to adenylate is found in both particulate and soluble fractions of tissue homogenates, and it is inhibited by pyrophosphate and ATP, as well as by caffeine, theophylline, and theobromine. These three methylated xanthines cause central nervous system and respiratory stimulation, smooth muscle relaxation, diuresis, coronary dilatation, cardiac stimulation, and skeletal muscle stimulation these effects are believed to be due to increased tissue concentrations of cyclic AMP resulting from inhibition of phosphodiesterase activity. 

Caffeine belongs to a family of naturally occurring compoimds called xanthines. The xanthines, in the form of their plant progenitors, are possibly the oldest known stimulants. They all, to varying extents, stimulate the central nervous system and the skeletal muscles. This stimulation results in an increased alertness, the ability to put off sleep, and an increased capacity for thinking. Caffeine is the most powerful xanthine in this respect. It is the main ingredient of the popular No-Doz keep-alert tablets. Although caffeine has a powerful effect on the central nervous system, not all xanthines are as effective. Thus, theobromine, the xanthine found in cocoa, has fewer central... 

These two methylated xanthines are found in quite a number of plants and have been extracted and widely used for centuries. Indeed, they very hkely have been, and remain today, the predominant stimulant consumed by humans. Every time you make a cup of tea or coffee, you perform an aqueous extraction of plant material (tea leaves. Camellia sinenis, 1 %, or coffee beans, Coffea spp., 1-2%) to obtain a dose of 25-100 mg of caffeine. Caffeine is also the active substance (—2%) in mate (used in Paraguay as a tea) made from the leaves of Ilex paraguensis. In coffee and tea, caffeine is the dominant member of the pair, whereas in Theobroma cacao, from which we obtain cocoa, theobromine (1-3%) is the primary source of the biological response. Caffeine acts to stimulate the central nervous system with its main impact on the cerebral cortex, and as it makes one more alert, it is no surprise that it is the chief constituent in No-Doz pills. 

The most well-known purine alkaloid is caffeine (1,3,7-trimethylxanthine) 1 which, along with theobromine (3,7-dimethylxanthine) 2, accumulates in leaves of tea and mate and beans of coffee and cacao, which are popular components of nonalcoholic beverages and/or chocolate products [2]. The pharmacological effects of purine alkaloids in animals, such as stimulation of the central nervous system, have been investigated extensively [3]. Caffeine is also often utilized in cytological studies to induce the formation of binucleate cells and is, therefore, used to measure the duration of the mitotic cycle [4]. 

The best known N-compound is caffeine (1,3,7-trimethylxanthine) because of its physiological effects (stimulation of the central nervous system, increased blood circulation and respiration). It is mildly bitter in taste (threshold value in water is 0.8-1.2 mmole/1), crystallizes with one molecule of water into silky, white needles, which melt at 236.5 °C and subhme without decomposition at 178 °C. The caffeine content of raw Arabica coffee is 0.9-1.4%, while in the Robusta variety, it is 1.5-2.6%. In contrast there are caffeine-free Coffea varieties. Santos, an Arabica coffee, is on the low side, while Robusta from Angola is at the top of the range given for caffeine content. Other purine alkaloids are theobromine (Arabica 36-40 mg/kg, Robusta 26-82 mg/kg)... 

Theobromine, the major alkaloid in cocoa, has similar pharmacological activities as caffeine. However, its stimulant activities on the central nervous system, respiration, and skeletal muscles are much weaker than those of caffeine, but its cardiac stimulant, coronary dilating, smooth muscle relaxant, and diuretic properties are stronger (Goodman and oilman). 

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