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 = | ImageFileL1 = Xanthine 3D ball.png | ImageClassL1 = bg-transparent | ImageFileR1 = Xanthine 3D spacefill.png | ImageClassR1 = bg-transparent | 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)C(=O)NC(=O)N2 | 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 = C₅H₄N₄O₂ | 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 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 stimulants 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 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 alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in the treatment of asthma or influenza symptoms.<ref name=pubchem/> 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.<ref name=pubchem/>

===Toxicity=== '''Methylxanthines''' (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 topically.<ref name=pubchem/>

===Pharmacology=== alt=|left|thumb|215x215px|class=skin-invert-image|Xanthine: R₁ = R₂ = R₃ = H<br>Caffeine: R₁ = R₂ = R₃ = CH₃<br>Theobromine: R₁ = H, R₂ = R₃ = CH₃<br>Theophylline: R₁ = R₂ = CH₃, R₃ = H In in vitro pharmacological studies, xanthines act as both competitive nonselective phosphodiesterase inhibitors and nonselective adenosine receptor antagonists. Phosphodiesterase inhibitors raise intracellular cAMP, activate PKA, 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 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 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!!R₁!!R₂!!R₃!!R₈!!IUPAC nomenclature!!Found in |- | Xanthine||H||H||H||H||3,7-Dihydro-purine-2,6-dione||Plants, animals |- | 7-Methylxanthine||H||H||CH₃||H||7-methyl-3''H''-purine-2,6-dione||Metabolite of caffeine and theobromine |- | Theobromine||H||CH₃||CH₃||H||3,7-Dihydro-3,7-dimethyl-1''H''-purine-2,6-dione||Cacao (chocolate), yerba mate, kola, guayusa |- | Theophylline||CH₃||CH₃||H||H||1,3-Dimethyl-7''H''-purine-2,6-dione||Tea, cacao (chocolate), yerba mate, kola |- | Paraxanthine||CH₃||H||CH₃||H||1,7-Dimethyl-7''H''-purine-2,6-dione||Animals that have consumed caffeine |- | Caffeine||CH₃||CH₃||CH₃||H||1,3,7-Trimethyl-1''H''-purine-2,6(3''H'',7''H'')-dione||Coffee, guarana, yerba mate, tea, kola, guayusa, Cacao (chocolate) |- | 8-Chlorotheophylline||CH₃||CH₃||H||Cl|| 8-Chloro-1,3-dimethyl-7''H''-purine-2,6-dione | Synthetic pharmaceutical ingredient |- | 8-Bromotheophylline||CH₃||CH₃||H||Br|| 8-Bromo-1,3-dimethyl-7''H''-purine-2,6-dione | Pamabrom diuretic medication |- |Diprophylline |CH₃ |CH₃ |C₃H₇O₂ |H |7-(2,3-Dihydroxypropyl)-1,3-dimethyl-3,7-dihydro-1''H''-purine-2,6-dione |Synthetic pharmaceutical ingredient |- |IBMX |CH₃ |C₄H₉ |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 disorders, 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 ¹²C/¹³C isotopic ratios of organic compounds found in the Murchison meteorite, suggested that xanthine and related chemicals, including the RNA component uracil, have been formed 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=AFP Staff |title=We may all be space aliens: study |date=13 June 2008 |url=http://afp.google.com/article/ALeqM5j_QHxWNRNdiW35Qr00L8CkwcXyvw |publisher=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.|author5-link=Jennifer Stern | 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 |archive-date=2015-06-23 |archive-url=https://web.archive.org/web/20150623004556/http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |url-status=dead }}</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