Xanthine


Xanthine is a purine base found in most human body tissues and fluids and in other organisms. Several stimulants are derived from xanthine, including caffeine, theophyline, and theobromine.
Xanthine is a product on the pathway of purine degradation.
Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme.

Use and manufacturing

Xanthine is used as a drug precursor for human and animal medications, and is manufactured as a pesticide ingredient.

Clinical significance

Derivatives of xanthine are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in the treatment of asthma or influenza symptoms. In contrast to other, more potent stimulants like sympathomimetic amines, xanthines mainly act to oppose the actions of adenosine, and increase alertness in the central nervous system.

Toxicity

Due to widespread effects, the therapeutic range of xanthine is narrow, making it a merely second-line asthma treatment. The therapeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia.
Methylated xanthines, which include caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline, theobromine, and theophylline, affect not only the airways but stimulate heart rate, force of contraction, and cardiac arrhythmias at high concentrations. In high doses, they can lead to convulsions that are resistant to anticonvulsants. Methylxanthines induce gastric acid and pepsin secretions in the gastrointestinal tract. Methylxanthines are metabolized by cytochrome P450 in the liver.
If swallowed, inhaled, or exposed to the eyes in high amounts, xanthines can be harmful, and may cause an allergic reaction if applied topically.

Pharmacology

In in vitro pharmacological studies, xanthines act as both:
  1. competitive nonselective phosphodiesterase inhibitors which raise intracellular cAMP, activate PKA, inhibit TNF-α and leukotriene synthesis, and reduce inflammation and innate immunity and
  2. nonselective adenosine receptor antagonists which inhibit sleepiness-inducing adenosine.
However, different analogues show varying potency at the numerous subtypes, and a wide range of synthetic xanthines have been developed searching for compounds with greater selectivity for phosphodiesterase enzyme or adenosine receptor subtypes.
NameR1R2R3R8IUPAC nomenclatureFound in
XanthineHHHH3,7-Dihydro-purine-2,6-dionePlants, animals
CaffeineCH3CH3CH3H1,3,7-Trimethyl-1H-purine-2,6-dioneCoffee, guarana, yerba mate, tea, kola, guayusa, holly
TheobromineHCH3CH3H3,7-Dihydro-3,7-dimethyl-1H-purine-2,6-dioneCacao, yerba mate, kola, guayusa, holly
TheophyllineCH3CH3HH1,3-Dimethyl-7H-purine-2,6-dioneTea, cacao, yerba mate, kola
ParaxanthineCH3HCH3H1,7-Dimethyl-7H-purine-2,6-dioneAnimals that have consumed caffeine
8-ChlorotheophyllineCH3CH3HCl8-Chloro-1,3-dimethyl-7H-purine-2,6-dioneSynthetic pharmaceutical ingredient
8-BromotheophyllineCH3CH3HBr8-Bromo-1,3-dimethyl-7H-purine-2,6-dionePamabrom diuretic medication
DiprophyllineCH3CH3C3H7O2H7--1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dioneSynthetic pharmaceutical ingredient
IBMXCH3C4H9HH1-Methyl-3--7H-purine-2,6-dione
Uric acidHHHO7,9-Dihydro-1H-purine-2,6,8-trioneByproduct of purine nucleotides metabolism and a normal component of urine

Pathology

People with the rare genetic disorders, specifically xanthinuria and Lesch–Nyhan syndrome, lack sufficient xanthine oxidase and cannot convert xanthine to uric acid.

Speculation on origin

Studies reported in 2008, based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, suggested that xanthine and related chemicals, including the RNA component uracil, were formed extraterrestrially. In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting xanthine and related organic molecules, including the DNA and RNA components adenine and guanine, were found in outer space.