Editing Phosphodiesterase inhibitor (section)

===Nonselective PDE inhibitors===
Methylated [[xanthines]] and derivatives:<ref name="PDEs-Essayan">{{cite journal | author=Essayan DM. | title=Cyclic nucleotide phosphodiesterases. | journal=The Journal of Allergy and Clinical Immunology | year=2001 | pages=671–80 | volume=108 | issue=5 | pmid=11692087 | doi=10.1067/mai.2001.119555 | doi-access=free }}</ref>
*[[caffeine]], a minor [[stimulant]]
*[[aminophylline]]
*[[IBMX]] (3-isobutyl-1-methylxanthine), used as investigative tool in pharmacological research
*[[paraxanthine]]
*[[pentoxifylline]], a drug that has the potential to enhance circulation and may have applicability in treatment of diabetes, fibrotic disorders, peripheral nerve damage, and microvascular injuries<ref name="PTX-Deree">{{cite journal | vauthors=Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R | title=Insights into the Regulation of TNF-α 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]]
*[[theophylline]], a [[bronchodilator]]
Methylated [[xanthines]] act as both
# competitive nonselective [[phosphodiesterase inhibitors]],<ref name="PDEs-Essayan"/> which raise intracellular [[Cyclic adenosine monophosphate|cAMP]], activate [[cAMP-dependent protein kinase|PKA]], [[TNF inhibitor|inhibit TNF-alpha]]<ref name="PTX-Deree"/><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> 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=Journal of Immunology | year=2005 | pages=589–94 | volume=174 | issue=2 | pmid=15634873 | doi=10.4049/jimmunol.174.2.589 | doi-access=free }}</ref> synthesis, and [[Anti-inflammatory|reduce inflammation]] and [[innate immunity]]<ref name="LT-Peters-Golden"/> and
# nonselective [[adenosine receptor]] antagonists<ref name="AR-Daly">{{cite journal | vauthors =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>
But different analogues show varying potency at the numerous subtypes, and a wide range of synthetic [[xanthine|xanthine derivatives]] (some nonmethylated) have been developed in the search for compounds with greater selectivity for [[phosphodiesterase|phosphodiesterase enzyme]] or [[adenosine receptor]] subtypes.<ref>{{cite journal | last1 = MacCorquodale | first1 = DW | title = The Synthesis of Some Alkylxanthines1,2 | date = July 1929 | journal = Journal of the American Chemical Society | volume = 51 | issue = 7| pages = 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] {{Webarchive|url=https://web.archive.org/web/20110805103634/http://www.wipo.int/pctdb/en/wo.jsp?amp%3BIA=WO1985%2F02540&%3BDISPLAY=DESC&IA=US1984002035&WO=1985%2F02540&DISPLAY=CLAIMS |date=2011-08-05 }}, 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 | 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="pmid2456442">{{cite journal | vauthors = 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 =https://zenodo.org/record/1253962 }}<!--https://zenodo.org/record/1253962--></ref><ref name="pmid2724296">{{cite journal | vauthors = 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 |date=June 1989 | pmid = 2724296 | doi = 10.1021/jm00126a014}}</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}}<!--https://zenodo.org/record/1235428--></ref><ref name="pmid7680859">{{cite journal | vauthors = Ukena D, Schudt C, Sybrecht GW | title = Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes | journal = [[Biochemical Pharmacology (journal)|Biochemical Pharmacology]] | volume = 45 | issue = 4 | pages = 847–51 |date=February 1993 | pmid = 7680859 | doi = 10.1016/0006-2952(93)90168-V}}</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 | date = July 2000 | pmid = 10869699 | doi = 10.1016/S0165-1838(00)00110-7 | url = https://zenodo.org/record/1259863 }}</ref><ref name="pmid17514358">{{cite journal | author = Daly JW | title = Caffeine analogs: biomedical impact | journal = Cellular and Molecular Life Sciences | volume = 64 | issue = 16 | pages = 2153–69 |date=August 2007 | pmid = 17514358 | doi = 10.1007/s00018-007-7051-9 | s2cid = 9866539 | url =  https://zenodo.org/record/1232583| pmc = 11138448 }}<!--https://zenodo.org/record/1232583--></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>