Xanthine /methylxanthines actions

All the xanthines, but especially theophylline, are capable of producing some degree of diuresis in humans. This specific action of the methylxanthines is discussed in greater detail in Chapter 21. 

The methylxanthine molecule is built on a foundation common to many biologic compounds, the xanthine double ring of carbons. The three methylxanthines, caffeine, theophylline, and theobromine, all block the action of the body s adenosine molecule, sending a signal that helps slow the chemical buildup inside cells. Because the methylxanthines closely resemble adenosine at the molecular level, they can occupy the molecular sites on cells that normally recognize, and react to, adenosine. Caffeine prevents the normal slowing action of adenosine at the cellular level, in both nerves and muscle. 

On the other hand, a new mode of action is sometimes discovered for an existing substance. If further substances are developed with a similar mode of action, the question arises whether a new stem is needed, which would mean modifying the old name for the first compound in the series. For example, albifylline and pentoxifylline are N-methylxanthine derivatives and the stem -fylline was therefore chosen for their names. These substances have been found to also suppress tumor necrosis factor-a. The experts decided to retain the stem fylline in this case, since the new action was nevertheless based on the typical xanthine-mediated inhibition of phosphodiesterase. 

Dyphylline is a xanthine derivative related to theophylline. It relaxes bronchial smooth muscle and stimulates central respiratory drive. It is indicated in the relief of acute bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema. A large number of derivatives of the methylxanthines have been prepared and examined for their ability to inhibit cyclic nucleotide phosphodiesterases (PDFs) and antagonize receptor-mediated actions of adenosine, the two best characterized cellular actions of the methylxanthines. Although certain modifications dissociate these two activities to some degree, these compounds are not used therapeutically. 

Caffeine, theobromine, and theophylline are purine derivatives closely related to the xanthine bodies found in the urine and tissues of animals. Xanthine is 2 6 dioxypurine caffeine is 1 3 7 trimethylxanthine theobromine is 3 7 di-methylxanthine and theophylline is 1 3 dimethylxanthine. They aU 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 CNS stimulant of the group theobromine... 

Experiments with liver slices and cultured cell lines have corroborated this pathway of purine degradation. In human liver slices 16 xanthine derivatives were produced from caffeine by action of P-450 system. Demethylation at N-3 was the most prominent process [18, 19]. Comparison of cell lines from humans, hamsters, mice, and rats show some interspecies differences but all of them demethylated and oxidized caffeine [20]. Human liver cells give 1,3,7-trimethylurate as the major metabolite of caffeine, but also made were the intermediate products theobromine, theophylline, and paraxanthine [21]. Human liver microsomes convert theophylline to 1-methylxanthine, 3-methylxanthine, and 1,3-dimethyluric acid [22, 23]. Human kidney microsomes produced each of the three possible demethylated products as well as 1,3,7-... 

It resists oxidizing and hydrating actions obstinately. Nitrous acid, however, converts it into hypoxanthln. Adenin is a poly-mere of hydrocyanic acid, and when heated to 200° (392° P.) it produces potassium cyanid. It has not been obtained synthetically from hydrocyanic acid, although the closely related xanthin and methylxanthin have been, formed by heating hydrocyanic acid, water and acetic acid together under pressure. 

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