View source for Xanthine

{{Distinguish|Xanthene|Xanthan}}
{{chembox
| Verifiedfields = changed
| verifiedrevid = 410178132
| Reference = <ref>''Merck Index'', 11th Edition, '''9968'''.</ref>
| ImageFile = Xanthin - Xanthine.svg
| ImageClass = skin-invert-image
| ImageSize = 
| ImageFile2 = Xanthine-3D-balls.png
| PIN = 3,7-Dihydro-1''H''-purine-2,6-dione
| OtherNames = 1''H''-Purine-2,6-dione
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4557
| Abbreviations = 
| InChI = 1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11)
| InChIKey1 = LRFVTYWOQMYALW-UHFFFAOYSA-N
| InChI1 = 1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11)
| CASNo = 69-89-6
| CASNo_Ref = {{cascite|correct|CAS}}
| EINECS = 
| PubChem = 1188
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1151
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB02134
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 1AVZ07U9S7
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = LRFVTYWOQMYALW-UHFFFAOYSA-N
| SMILES = c1[nH]c2c(n1)nc(nc2O)O
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1424
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11)
| RTECS =
| MeSHName =
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 17712
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C00385
 }}
|Section2={{Chembox Properties
| Formula = C<sub>5</sub>H<sub>4</sub>N<sub>4</sub>O<sub>2</sub>
| MolarMass = 152.11 g/mol
| Appearance = White solid
| Density = 
| MeltingPt = decomposes
| MeltingPt_notes =
| BoilingPt = 
| BoilingPt_notes = 
| Solubility = 1 g/ 14.5 L @ 16 °C<br>1 g/1.4 L @ 100 °C
| SolubleOther = 
| Solvent = 
| pKa = 
| pKb = }}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = 
| ATCCode_suffix = 
| ATC_Supplemental =
 }}
|Section7={{Chembox Hazards
| MainHazards = 
| NFPA-H = 2
| NFPA-F = 1
| NFPA-R = 0
| NFPA-S =
| HPhrases = 
| PPhrases = 
| GHS_ref  = 
| FlashPt = 
| AutoignitionPt = 
| ExploLimits = 
| PEL = 
 }}
}}
'''Xanthine''' ({{IPAc-en|ˈ|z|æ|n|θ|iː|n}} or {{IPAc-en|ˈ|z|æ|n|θ|aɪ|n}}, from [[Ancient Greek]] {{Lang|grc|ξανθός}} {{Lang|grc-latn|xanthós}} {{Gloss|yellow}} for its yellowish-white appearance; archaically '''xanthic acid'''; systematic name '''3,7-dihydropurine-2,6-dione''') is a [[purine]] [[base (genetics)|base]] found in most human body tissues and fluids, as well as in other organisms.<ref name="pubchem">{{cite web |title=Xanthine, CID 1188 |url=https://pubchem.ncbi.nlm.nih.gov/compound/1188 |publisher=PubChem, National Library of Medicine, US National Institutes of Health |access-date=28 September 2019 |date=2019}}</ref> Several [[stimulant]]s are derived from xanthine, including [[caffeine]], [[theophylline]], and [[theobromine]].<ref name="isbn0-8493-2647-8">{{cite book | author = Spiller, Gene A. | title = Caffeine | publisher = CRC Press | location = Boca Raton | year = 1998 | isbn = 0-8493-2647-8 }}</ref><ref name=":0">{{Cite book|last=Katzung|first=Bertram G.|title=Basic & Clinical Pharmacology|publisher=Paramount Publishing|year=1995|isbn=0-8385-0619-4|location=East Norwalk, Connecticut|pages=310, 311}}</ref>

Xanthine is a product on the pathway of [[purine degradation]].<ref name=pubchem/>
* It is created from [[guanine]] by [[guanine deaminase]].
* It is created from [[hypoxanthine]] by [[xanthine oxidoreductase]].
* It is also created from [[xanthosine]] by [[purine nucleoside phosphorylase]].

Xanthine is subsequently converted to [[uric acid]] by the action of the [[xanthine oxidase]] enzyme.<ref name=pubchem/>

==Use and production==
Xanthine is used as a [[drug]] [[precursor (chemistry)|precursor]] for human and animal medications, and is produced as a [[pesticide]] ingredient.<ref name=pubchem/>

==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]] 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/>

==Possible formation in absence of life==

Studies reported in 2008, based on <sup>12</sup>C/<sup>13</sup>C [[isotopic ratio]]s of [[organic compounds]] found in the [[Murchison meteorite]], suggested that xanthine and related chemicals, including the [[RNA]] component [[uracil]], have been formed [[Extraterrestrial materials|extraterrestrially]].<ref name="Murch_base">{{Cite journal | last1 = Martins | first1 = Z. | last2 = Botta | first2 = O. | last3 = Fogel | first3 = M. L. | last4 = Sephton | first4 = M. A. | last5 = Glavin | first5 = D. P. | last6 = Watson | first6 = J. S. | last7 = Dworkin | first7 = J. P. | last8 = Schwartz | first8 = A. W. | last9 = Ehrenfreund | first9 = P. | title = Extraterrestrial nucleobases in the Murchison meteorite | doi = 10.1016/j.epsl.2008.03.026 | journal = Earth and Planetary Science Letters | volume = 270 | issue = 1–2 | pages=130–136 | year = 2008 | bibcode=2008E&PSL.270..130M|arxiv = 0806.2286 | s2cid = 14309508 }}</ref><ref>{{Cite web|author=[[Agence France-Presse|AFP]] Staff |title=We may all be space aliens: study |date=13 June 2008 |url=http://afp.google.com/article/ALeqM5j_QHxWNRNdiW35Qr00L8CkwcXyvw |publisher=[[Agence France-Presse|AFP]] |access-date=2011-08-14 |url-status=dead |archive-url=https://web.archive.org/web/20080617213441/http://afp.google.com/article/ALeqM5j_QHxWNRNdiW35Qr00L8CkwcXyvw |archive-date=June 17, 2008 }}</ref> 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]].<ref name="Callahan">{{Cite journal | last1 = Callahan | first1 = M. P. | last2 = Smith | first2 = K. E. | last3 = Cleaves | first3 = H. J. | last4 = Ruzicka | first4 = J. | last5 = Stern | first5 = J. C. | last6 = Glavin | first6 = D. P. | last7 = House | first7 = C. H. | last8 = Dworkin | first8 = J. P. | doi = 10.1073/pnas.1106493108 | title = Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases | journal = Proceedings of the National Academy of Sciences | volume = 108 | issue = 34 | pages = 13995–8 | year = 2011 | pmid = 21836052| pmc = 3161613| bibcode = 2011PNAS..10813995C | doi-access = free }}</ref><ref name="Steigerwald">{{cite web |last=Steigerwald |first=John |title=NASA Researchers: DNA Building Blocks Can Be Made in Space |url=http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |publisher=[[NASA]] |date=8 August 2011 |access-date=2011-08-10 }}</ref><ref name="DNA">{{cite web |author=ScienceDaily Staff |title=DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests |url=https://www.sciencedaily.com/releases/2011/08/110808220659.htm |date=9 August 2011 |website=[[ScienceDaily]] |access-date=2011-08-09}}</ref>

== See also ==
* [[DMPX]]
* [[Murchison meteorite]]
* [[Theobromine poisoning]]
* [[Xanthene]]
* [[Xanthone]]
* [[Xanthydrol]]
* [[Kidney stone disease]]

==References==
{{Reflist}}

{{Stimulants}}
{{Asthma and copd rx}}
{{Nucleotide metabolism intermediates}}
{{Adenosine receptor modulators}}
{{Chemical classes of psychoactive drugs}}

[[Category:Xanthines| ]]
[[Category:Enones]]