View source for Xanthine

==Clinical significance==
Derivatives of xanthine (known collectively as '''xanthines''') are a group of [[alkaloid]]s commonly used for their effects as mild [[stimulant]]s and as [[bronchodilator]]s, notably in the treatment of [[asthma]] or [[influenza]] symptoms.<ref name=pubchem/> In contrast to other, more potent stimulants like [[sympathomimetic amine]]s, xanthines mainly act to oppose the actions of [[adenosine]], and increase alertness in the [[central nervous system]].<ref name=pubchem/>

===Toxicity===
'''Methylxanthines''' ([[Methylation|methylated]] xanthines), which include [[caffeine]], [[aminophylline]], [[IBMX]], [[paraxanthine]], [[pentoxifylline]], [[theobromine]], [[theophylline]], and [[7-methylxanthine]] (heteroxanthine), among others, affect the airways, increase heart rate and force of contraction, and at high concentrations can cause cardiac arrhythmias.<ref name=pubchem/> In high doses, they can lead to convulsions that are resistant to anticonvulsants.<ref name=pubchem/>  Methylxanthines induce [[gastric acid]] and [[pepsin]] secretions in the [[gastrointestinal tract]].<ref name=pubchem/>  Methylxanthines are metabolized by [[cytochrome P450]] enzymes in the liver.<ref name=pubchem/>

If swallowed, inhaled, or exposed to the eyes in high amounts, xanthines can be harmful, and they may cause an [[allergic reaction]] if applied [[topical medication|topically]].<ref name=pubchem/>

===Pharmacology=== 
[[File:Methylxanthine.png|alt=|left|thumb|215x215px|class=skin-invert-image|Xanthine: R<sub>1</sub> = R<sub>2</sub> = R<sub>3</sub> = H<br>Caffeine: R<sub>1</sub> = R<sub>2</sub> = R<sub>3</sub> = CH<sub>3</sub><br>Theobromine: R<sub>1</sub> = H, R<sub>2</sub> = R<sub>3</sub> = CH<sub>3</sub><br>Theophylline: R<sub>1</sub> = R<sub>2</sub> = CH<sub>3</sub>, R<sub>3</sub> = H]]
In [[in vitro]] [[pharmacology|pharmacological]] studies, xanthines act as both competitive nonselective [[phosphodiesterase inhibitors]] and nonselective [[adenosine receptor]] antagonists. [[Phosphodiesterase inhibitors]] raise intracellular [[Cyclic adenosine monophosphate|cAMP]], activate [[cAMP-dependent protein kinase|PKA]], [[TNF inhibitor|inhibit TNF-α]] synthesis,<ref name=pubchem/><ref name="pmid9927365">{{cite journal |vauthors=Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U |title=Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages |journal=Am. J. Respir. Crit. Care Med. |volume=159 |issue=2 |pages=508–11 |date=February 1999 |pmid=9927365 |doi= 10.1164/ajrccm.159.2.9804085}}</ref><ref name=":0" /> and [[leukotriene]]<ref name="LT-Peters-Golden">{{cite journal |vauthors=Peters-Golden M, Canetti C, Mancuso P, Coffey MJ | title=Leukotrienes: underappreciated mediators of innate immune responses | journal=J. Immunol. | year=2005 | pages=589–94 | volume=174 | issue=2 | pmid=15634873 | doi=10.4049/jimmunol.174.2.589| doi-access=free }}</ref> and [[Anti-inflammatory|reduce inflammation]] and [[innate immunity]].<ref name="LT-Peters-Golden"/> [[Adenosine receptor]] antagonists<ref name="pmid3588607"/> inhibit sleepiness-inducing [[adenosine]].<ref name=pubchem/>

However, 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|phosphodiesterase enzyme]] or [[adenosine receptor]] subtypes.<ref name=pubchem/><ref name="pmid3806581">{{cite journal |vauthors=Daly JW, Padgett WL, Shamim MT | title = Analogues of caffeine and theophylline: effect of structural alterations on affinity at adenosine receptors | journal = Journal of Medicinal Chemistry | volume = 29 | issue = 7 | pages = 1305–8 |date=July 1986 | pmid = 3806581 | doi = 10.1021/jm00157a035}}</ref><ref name="pmid3588607">{{cite journal |vauthors=Daly JW, Jacobson KA, Ukena D | title = Adenosine receptors: development of selective agonists and antagonists | journal = Progress in Clinical and Biological Research | volume = 230 | pages = 41–63 | year = 1987 | pmid = 3588607 }}</ref><ref name="pmid1658821">{{cite journal |vauthors=Daly JW, Hide I, Müller CE, Shamim M | title = Caffeine analogs: structure-activity relationships at adenosine receptors | journal = Pharmacology | volume = 42 | issue = 6 | pages = 309–21 | year = 1991 | pmid = 1658821 | doi = 10.1159/000138813| url = https://zenodo.org/record/1235428}}</ref><ref name="pmid17668454">{{cite journal |vauthors=González MP, Terán C, Teijeira M | title = Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we? | journal = Medicinal Research Reviews | volume = 28 | issue = 3 | pages = 329–71 |date=May 2008 | pmid = 17668454 | doi = 10.1002/med.20108 | s2cid = 23923058 }}</ref><ref name="pmid18181659">{{cite journal |vauthors=Baraldi PG, Tabrizi MA, Gessi S, Borea PA | title = Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility | journal = Chemical Reviews | volume = 108 | issue = 1 | pages = 238–63 |date=January 2008 | pmid = 18181659 | doi = 10.1021/cr0682195 }}</ref>

{| class="wikitable sortable"
|+ Examples of xanthine derivatives
!Name!!R<sub>1</sub>!!R<sub>2</sub>!!R<sub>3</sub>!!R<sub>8</sub>!![[IUPAC nomenclature]]!!Found in
|-
| Xanthine||H||H||H||H||3,7-Dihydro-purine-2,6-dione||Plants, animals
|-
| [[7-Methylxanthine]]||H||H||[[Methyl group|CH<sub>3</sub>]]||H||7-methyl-3''H''-purine-2,6-dione||Metabolite of caffeine and theobromine
|-
| [[Theobromine]]||H||CH<sub>3</sub>||CH<sub>3</sub>||H||3,7-Dihydro-3,7-dimethyl-1''H''-purine-2,6-dione||[[Cocoa bean|Cacao]] ([[chocolate]]),   [[yerba mate]], [[Kola nut|kola]], [[guayusa]]
|-
| [[Theophylline]]||CH<sub>3</sub>||CH<sub>3</sub>||H||H||1,3-Dimethyl-7''H''-purine-2,6-dione||[[Tea]], [[Cocoa bean|cacao]] ([[chocolate]]), [[yerba mate]], [[Kola nut|kola]]
|-
| [[Paraxanthine]]||CH<sub>3</sub>||H||CH<sub>3</sub>||H||1,7-Dimethyl-7''H''-purine-2,6-dione||Animals that have consumed caffeine
|-
| [[Caffeine]]||CH<sub>3</sub>||CH<sub>3</sub>||CH<sub>3</sub>||H||1,3,7-Trimethyl-1''H''-purine-2,6(3''H'',7''H'')-dione||[[Coffee]], [[guarana]], [[yerba mate]], [[tea]], [[Kola nut|kola]], [[guayusa]], [[Cocoa bean|Cacao]] ([[chocolate]])
|-
| [[8-Chlorotheophylline]]||CH<sub>3</sub>||CH<sub>3</sub>||H||[[Chloride|Cl]]|| 8-Chloro-1,3-dimethyl-7''H''-purine-2,6-dione
| Synthetic pharmaceutical ingredient
|-
| [[8-Bromotheophylline]]||CH<sub>3</sub>||CH<sub>3</sub>||H||[[Bromide|Br]]|| 8-Bromo-1,3-dimethyl-7''H''-purine-2,6-dione
| [[Pamabrom]] diuretic medication
|-
|[[Diprophylline]]
|CH<sub>3</sub>
|CH<sub>3</sub>
|C<sub>3</sub>H<sub>7</sub>O<sub>2</sub>
|H
|7-(2,3-Dihydroxypropyl)-1,3-dimethyl-3,7-dihydro-1''H''-purine-2,6-dione
|Synthetic pharmaceutical ingredient
|-
|[[IBMX]]
|CH<sub>3</sub>
|[[Butyl group|C<sub>4</sub>H<sub>9</sub>]]
|H
|H
|1-Methyl-3-(2-methylpropyl)-7''H''-purine-2,6-dione
|
|-
|[[Uric acid]]
|H
|H
|H
|O
|7,9-Dihydro-1''H''-purine-2,6,8(3''H'')-trione
|Byproduct of [[purine]] nucleotides metabolism and a normal component of urine
|}
{{Clear}}

===Pathology===
People with rare [[genetic disorder]]s, specifically [[xanthinuria]] and [[Lesch–Nyhan syndrome]], lack sufficient xanthine oxidase and cannot convert xanthine to [[uric acid]].<ref name=pubchem/>