Xanthine (pronounced /ˈzænθiːn/ or /ˈzænθaɪn/), (3,7-dihydro-purine-2,6-dione), is a purine base found in most human body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine.
Xanthine is a product on the pathway of purine degradation.
* It is created from guanine by guanine deaminase.
* It is created from hypoxanthine by xanthine oxidoreductase.
Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme.
People with the rare genetic disorder xanthinuria lack sufficient xanthine oxidase and cannot convert xanthine to uric acid.
Clinical significance of xanthine derivatives
Derivatives of xanthine, known collectively as xanthines, are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in treating the symptoms of asthma. In contrast to other, more potent stimulants, they only inhibit the actions of sleepiness-inducing adenosine, making them somewhat less effective as stimulants than sympathomimetic amines. Due to widespread effects, the therapeutic range of xanthines is narrow, making them merely a second-line asthma treatment. The therapeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia.
Methylxanthines affect not only the airways but stimulates heart rate, force of contraction, cardiac arrhythmias at high concentrations. In the CNS they increase alertness, stimulate the respiratory centre, and are used for treatment of infantile apnea. In high doses they can lead to convulsions that are resistant to anticonvulsants. Methylxanthines induce acid and pepsin secretions in the GI tract. Methylxanthines are metabolized by Cytochrome P450 in the liver. Methylated xanthines include caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline , theobromine, and theophylline. These drugs act as both
1. competitive nonselective phosphodiesterase inhibitors  which raise intracellular cAMP, activate PKA, inhibit TNF-alpha   and leukotriene  synthesis, and reduce inflammation and innate immunity  and
2. nonselective adenosine receptor antagonists  which inhibit sleepiness-inducing adenosine.
But different analogues show varying potency at the numerous subtypes, and a wide range of synthetic xanthines (some nonmethylated) have been developed searching for compounds with greater selectivity for phosphodiesterase enzyme or adenosine receptor subtypes. Xanthines are also found very rarely as constituents of nucleic acids.
Caffeine: R1 = R2 = R3 = CH3
Theobromine: R1 = H, R2 = R3 = CH3
Theophylline: R1 = R2 = CH3, R3 = H
Selected Xanthines Name↓ R1↓ R2↓ R3↓ IUPAC nomenclature↓ Found In↓
Caffeine CH3 CH3 CH3 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione Coffee, Guarana, Yerba mate, Tea, Kola
Theobromine H CH3 CH3 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione Chocolate, Yerba mate
Theophylline CH3 CH3 H 1,3-dimethyl-7H-purine-2,6-dione Tea, Yerba mate
Xanthine H H H 3,7-dihydro-purine-2,6-dione plants, animals
* Murchison meteorite
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