Xanthine: Difference between revisions

{{distinguish|xanthene}}

| verifiedrevid = 410176309

| reference = <ref>''Merck Index'', 11th Edition, '''9968'''.</ref>

| IUPACName = 3,7-Dihydropurine-2,6-dione

| OtherNames = 1''H''-Purine-2,6-diol

| Section1 = {{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|CAS}}= {{cascite|??|??}}

| PubChem = 1188

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| SMILES = c1[nH]c2c(n1)nc(nc2O)O

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| StdInChI = 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)

| ChEBI =

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG =

| ATCCode_prefix =

| ATCCode_suffix =

| ATC_Supplemental =}}

| Section2 = {{Chembox Properties

| Melting_notes =

| Boiling_notes =

| Section7 = {{Chembox Hazards

| EUClass =

| EUIndex =

| NFPA-H =

| NFPA-F =

| NFPA-R =

| NFPA-O =

| RPhrases =

| SPhrases =

| RSPhrases =

| Autoignition =

| PEL = }}

'''Xanthine''' ({{pron-en|ˈzænθiːn}} or {{IPA-en|ˈzænθaɪn|}}), (3,7-dihydro-purine-2,6-dione), is a [[purine]] [[base (chemistry)|base]] found in most human body tissues and fluids and in other organisms. A number of mild [[stimulant]]s are derived from xanthine, including [[caffeine]] and [[theobromine]].<ref name="isbn0-8493-2647-8">{{cite book | author = Spiller, Gene A. | authorlink = | editor = | others = | title = Caffeine | edition = | language = | publisher = CRC Press | location = Boca Raton | year = 1998 | origyear = | pages = | quote = | isbn = 0-8493-2647-8 | oclc = | doi = | url = | accessdate = }}</ref>

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.

==Pathology==

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 [[alkaloid]]s commonly used for their effects as mild [[stimulant]]s and as [[bronchodilator]]s, 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 amine]]s. 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 stimulate 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.

[[Methylation|Methylated]] xanthines include [[caffeine]], [[aminophylline]], [[IBMX]], [[paraxanthine]], [[pentoxifylline]] <ref name="PTX-Deree">{{cite journal | author=Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R. | title=Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition. | journal=Clinics (Sao Paulo). | year=2008 | pages=321–8 | volume=63 | issue=3 | pmid=18568240 | doi=10.1590/S1807-59322008000300006 | pmc=2664230 }}</ref>, [[theobromine]], and [[theophylline]]. These drugs act as both

# competitive nonselective [[phosphodiesterase inhibitors]] <ref name="PDEs-Essayan">{{cite journal | author=Essayan DM. | title=Cyclic nucleotide phosphodiesterases. | journal=J Allergy Clin Immunol. | year=2001 | pages=671–80 | volume=108 | issue=5 | pmid=11692087 | doi=10.1067/mai.2001.119555 }}</ref> which raise intracellular [[Cyclic adenosine monophosphate|cAMP]], activate [[cAMP-dependent protein kinase|PKA]], [[TNF inhibitor|inhibit TNF-alpha]] <ref name="PTX-Deree">{{cite journal | author=Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R. | title=Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition. | journal=Clinics (Sao Paulo). | year=2008 | pages=321–8 | volume=63 | issue=3 | pmid=18568240 | doi=10.1590/S1807-59322008000300006 | pmc=2664230 }}</ref> <ref name="pmid9927365">{{cite journal |author=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 |year=1999 |month=February |pmid=9927365 |doi= |url=http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=9927365}}</ref> and [[leukotriene]] <ref name="LT-Peters-Golden">{{cite journal | author=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 | url=http://www.jimmunol.org/cgi/content/full/174/2/589 }}</ref> synthesis, and [[Anti-inflammatory|reduce inflammation]] and [[innate immunity]] <ref name="LT-Peters-Golden">{{cite journal | author=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 | url=http://www.jimmunol.org/cgi/content/full/174/2/589 }}</ref> and

# nonselective [[adenosine receptor]] antagonists <ref name="AR-Daly">{{cite journal | author=Daly JW, Jacobson KA, Ukena D. | title=Adenosine receptors: development of selective agonists and antagonists. | journal=Prog Clin Biol Res. | year=1987 | pages=:41–63 | volume=230 | issue=1 | pmid=3588607 }}</ref> 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|phosphodiesterase enzyme]] or [[adenosine receptor]] subtypes.<ref>MacCorquodale DW. THE SYNTHESIS OF SOME ALKYLXANTHINES. ''Journal of the American Chemical Society''. 1929 July;51(7):2245–2251. DOI: 10.1021/ja01382a042</ref><ref>[http://www.wipo.int/pctdb/en/wo.jsp?amp%3BIA=WO1985%2F02540&%3BDISPLAY=DESC&IA=US1984002035&WO=1985%2F02540&DISPLAY=CLAIMS WO patent 1985002540], Sunshine A, Laska EM, Siegel CE, "ANALGESIC AND ANTI-INFLAMMATORY COMPOSITIONS COMPRISING XANTHINES AND METHODS OF USING SAME", granted 1989-03-22 , assigned to RICHARDSON-VICKS, INC.</ref><ref name="US 4288433">{{Ref patent3 | country = US | number = 4288433 | status = granted | title = Cosmetic compositions having a slimming action | pubdate = 1979-09-24 | gdate = 1981-09-04 | pridate= 1979-09-24 | inventor = Constantin Koulbanis, Claude Bouillon, Patrick Darmenton | assign1= L'Oreal | google_patent_id = 96M6AAAAEBAJ }}</ref><ref name="pmid3806581">{{cite journal | author = 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 | year = 1986 | month = July | pmid = 3806581 | doi = 10.1021/jm00157a035| url = | issn = }}</ref><ref name="pmid3588607">{{cite journal | author = Daly JW, Jacobson KA, Ukena D | title = Adenosine receptors: development of selective agonists and antagonists | journal = Progress in Clinical and Biological Research | volume = 230 | issue = | pages = 41–63 | year = 1987 | pmid = 3588607 | doi = | url = | issn = }}</ref><ref name="pmid2456442">{{cite journal | author = Choi OH, Shamim MT, Padgett WL, Daly JW | title = Caffeine and theophylline analogues: correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors | journal = Life Sciences | volume = 43 | issue = 5 | pages = 387–98 | year = 1988 | pmid = 2456442 | doi = 10.1016/0024-3205(88)90517-6| url = | issn = }}</ref><ref name="pmid2724296">{{cite journal | author = Shamim MT, Ukena D, Padgett WL, Daly JW | title = Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di-, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions | journal = Journal of Medicinal Chemistry | volume = 32 | issue = 6 | pages = 1231–7 | year = 1989 | month = June | pmid = 2724296 | doi = 10.1021/jm00126a014| url = | issn = }}</ref><ref name="pmid1658821">{{cite journal | author = 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 = | issn = }}</ref><ref name="pmid7680859">{{cite journal | author = Ukena D, Schudt C, Sybrecht GW | title = Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes | journal = Biochemical Pharmacology | volume = 45 | issue = 4 | pages = 847–51 | year = 1993 | month = February | pmid = 7680859 | doi = 10.1016/0006-2952(93)90168-V| url = http://linkinghub.elsevier.com/retrieve/pii/0006-2952(93)90168-V | issn = }}</ref><ref name="pmid10869699">{{cite journal | author = Daly JW | title = Alkylxanthines as research tools | journal = Journal of the Autonomic Nervous System | volume = 81 | issue = 1-3 | pages = 44–52 | year = 2000 | month = July | pmid = 10869699 | doi = 10.1016/S0165-1838(00)00110-7| url = http://linkinghub.elsevier.com/retrieve/pii/S0165183800001107 | issn = }}</ref><ref name="pmid17514358">{{cite journal | author = Daly JW | title = Caffeine analogs: biomedical impact | journal = Cellular and Molecular Life Sciences : CMLS | volume = 64 | issue = 16 | pages = 2153–69 | year = 2007 | month = August | pmid = 17514358 | doi = 10.1007/s00018-007-7051-9 | url = | issn = }}</ref><ref name="pmid17668454">{{cite journal | author = 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 | year = 2008 | month = May | pmid = 17668454 | doi = 10.1002/med.20108 | url = | issn = }}</ref><ref name="pmid18181659">{{cite journal | author = 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 | year = 2008 | month = January | pmid = 18181659 | doi = 10.1021/cr0682195 | url = | issn = }}</ref> Xanthines are also found very rarely as constituents of [[nucleic acid]]s.

[[Image:Methylxanthin (R1, R2, R3).svg‎|200px|left|thumb|Caffeine: R₁ = R₂ = R₃ = CH₃<br>Theobromine: R₁ = H, R₂ = R₃ = CH₃<br>Theophylline: R₁ = R₂ = CH₃, R₃ = H]]

{{-}}

|+ Selected Xanthines

!Name!!R₁!!R₂!!R₃!![[IUPAC nomenclature]]!!Found In

|[[Caffeine]]||[[Methyl|CH₃]]||[[Methyl|CH₃]]||[[Methyl|CH₃]]||1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione||[[Coffee]], [[Guarana]], [[Yerba mate]], [[Tea]], [[Kola]]

|[[Theobromine]]||H||[[Methyl|CH₃]]||[[Methyl|CH₃]]||3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione||[[Chocolate]], [[Yerba mate]]

|[[Theophylline]]||[[Methyl|CH₃]]||[[Methyl|CH₃]]||H||1,3-dimethyl-7H-purine-2,6-dione||[[Tea]], [[chocolate]], [[Yerba mate]]

|Xanthine||H||H||H||3,7-dihydro-purine-2,6-dione||plants, animals

{{-}}

==See also==

* [[Xanthydrol]]

==References==

{{Reflist|colwidth=30em}}

{{Psychostimulants, agents used for ADHD and nootropics}}

[[bg:Ксантин]]

[[ca:Xantina]]

[[da:Xanthin]]

[[de:Xanthin]]

[[es:Xantina]]

[[fr:Xanthine]]

[[io:Xantino]]

[[id:Xantina]]

[[it:Xantina]]

[[mk:Ксантин]]

[[nl:Xanthine]]

[[ja:キサンチン]]

[[pl:Ksantyna]]

[[pt:Xantina]]

[[ru:Ксантин]]

[[fi:Ksantiini]]

[[sv:Xantin]]

[[ur:Xanthine]]

[[zh:黄嘌呤]]