Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and AM404: Difference between pages
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Saving copy of the {{drugbox}} taken from revid 460001893 of page AM404 for the Chem/Drugbox validation project (updated: 'CAS_number'). |
m Adding a hyperlink to knockout mice |
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{{Short description|Active metabolite of paracetamol}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid [{{fullurl:AM404|oldid=460001893}} 460001893] of page [[AM404]] with values updated to verified values.}} |
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{{missing information|history of discovery — who gave it this codename?|date=December 2022}} |
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{{Drugbox |
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{{Infobox drug |
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| image = AM404_skel.svg |
| image = AM404_skel.svg |
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| width = 240 |
| width = 240 |
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<!--Clinical data--> |
<!--Clinical data--> |
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| tradename = |
| tradename = |
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| legal_status = |
| legal_status = |
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| routes_of_administration = |
| routes_of_administration = |
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<!--Pharmacokinetic data--> |
<!--Pharmacokinetic data--> |
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| elimination_half-life = |
| elimination_half-life = |
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| excretion = |
| excretion = |
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<!--Identifiers--> |
<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = |
| CAS_number = 183718-77-6 |
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| CAS_supplemental = {{CAS|198022-70-7}} |
| CAS_supplemental = {{CAS|198022-70-7}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = XVJ94H0U21 |
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| PubChem = 6604822 |
| PubChem = 6604822 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 39878 |
| ChEMBL = 39878 |
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<!--Chemical data--> |
<!--Chemical data--> |
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| C=26 | H=37 | N=1 | O=2 |
| C=26 | H=37 | N=1 | O=2 |
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| molecular_weight = 395.577 g/mol |
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| smiles = O=C(Nc1ccc(O)cc1)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC |
| smiles = O=C(Nc1ccc(O)cc1)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC |
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| InChI = 1/C26H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-26(29)27-24-20-22-25(28)23-21-24/h6-7,9-10,12-13,15-16,20-23,28H,2-5,8,11,14,17-19H2,1H3,(H,27,29)/b7-6-,10-9-,13-12-,16-15- |
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| InChIKey = IJBZOOZRAXHERC-DOFZRALJBG |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C26H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-26(29)27-24-20-22-25(28)23-21-24/h6-7,9-10,12-13,15-16,20-23,28H,2-5,8,11,14,17-19H2,1H3,(H,27,29)/b7-6-,10-9-,13-12-,16-15- |
| StdInChI = 1S/C26H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-26(29)27-24-20-22-25(28)23-21-24/h6-7,9-10,12-13,15-16,20-23,28H,2-5,8,11,14,17-19H2,1H3,(H,27,29)/b7-6-,10-9-,13-12-,16-15- |
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| StdInChIKey = IJBZOOZRAXHERC-DOFZRALJSA-N |
| StdInChIKey = IJBZOOZRAXHERC-DOFZRALJSA-N |
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}} |
}} |
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'''AM404''', also known as '''''N''-arachidonoylphenolamine''',<ref name="Nakamura2022">{{cite journal | vauthors = Nakamura S, Nonaka T, Komatsu S, Yamada T, Yamamoto T | title = Oral acetaminophen-induced spinal 5-hydroxytriyptamine release produces analgesic effects in the rat formalin test | journal = Biomedicine & Pharmacotherapy | volume = 146 | pages = 112578 | date = February 2022 | pmid = 34959121 | doi = 10.1016/j.biopha.2021.112578 | s2cid = 245483361 | doi-access = free }}</ref><ref name="Rogosch2012">{{cite journal | vauthors = Rogosch T, Sinning C, Podlewski A, Watzer B, Schlosburg J, Lichtman AH, Cascio MG, Bisogno T, Di Marzo V, Nüsing R, Imming P | display-authors = 6 | title = Novel bioactive metabolites of dipyrone (metamizol) | journal = Bioorganic & Medicinal Chemistry | volume = 20 | issue = 1 | pages = 101–107 | date = January 2012 | pmid = 22172309 | pmc = 3248997 | doi = 10.1016/j.bmc.2011.11.028 }}</ref> is an [[active metabolite]] of [[paracetamol]] (acetaminophen), responsible for all or part of its [[analgesic]] action<ref name="pmid16438952">{{cite journal | vauthors = Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A | title = The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors | journal = European Journal of Pharmacology | volume = 531 | issue = 1–3 | pages = 280–281 | date = February 2006 | pmid = 16438952 | doi = 10.1016/j.ejphar.2005.12.015 }}</ref> and [[anticonvulsant]] effects.<ref name=":0">{{cite journal | vauthors = Deshpande LS, DeLorenzo RJ | title = Acetaminophen inhibits status epilepticus in cultured hippocampal neurons | journal = NeuroReport | volume = 22 | issue = 1 | pages = 15–18 | date = January 2011 | pmid = 21037491 | pmc = 3052417 | doi = 10.1097/WNR.0b013e3283413231 }}</ref> Chemically, it is the [[amide]] formed from [[4-Aminophenol|4-aminophenol]] and [[arachidonic acid]]. |
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== Pharmacology == |
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It is established that AM404 increases concentrations of the endogenous cannabinoid [[anandamide]] within the [[synapse|synaptic cleft]], contributing to its analgesic activity.<ref name="pmid15987694" /> This has been well characterised as involving [[endocannabinoid transporter]] inhibition, but the precise transporter responsible is yet to be determined.<ref name="pmid15987694" /><ref name=":1" /><ref name="pmid12655057" /> |
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AM404 was originally reported to be an [[endocannabinoid reuptake inhibitor|endogenous cannabinoid reuptake inhibitor]], preventing the transport of anandamide and other related compounds back from the [[synapse|synaptic cleft]], much in the same way that common [[selective serotonin reuptake inhibitor]] (SSRI) antidepressants prevent the reuptake of [[serotonin]]. Earlier work on the mechanism of AM404 suggested that the inhibition of [[fatty acid amide hydrolase]] (FAAH) by AM404 was responsible for all of its attributed reuptake properties, since intracellular FAAH hydrolysis of [[anandamide]] changes the intra/extracellular anandamide equilibrium.<ref name="pmid12655057">{{cite journal | vauthors = Glaser ST, Abumrad NA, Fatade F, Kaczocha M, Studholme KM, Deutsch DG | title = Evidence against the presence of an anandamide transporter | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 7 | pages = 4269–4274 | date = April 2003 | pmid = 12655057 | pmc = 153082 | doi = 10.1073/pnas.0730816100 | doi-access = free | bibcode = 2003PNAS..100.4269G }}</ref> However, this is not the case, as newer research on FAAH [[knockout mice]] has found that brain cells internalize anandamide through a selective transport mechanism which is independent of FAAH activity.<ref name=":1">{{cite journal | vauthors = Fegley D, Kathuria S, Mercier R, Li C, Goutopoulos A, Makriyannis A, Piomelli D | title = Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 23 | pages = 8756–8761 | date = June 2004 | pmid = 15138300 | pmc = 423268 | doi = 10.1073/pnas.0400997101 | doi-access = free | authorlink6 = Alexandros Makriyannis }}</ref> It is this mechanism which is inhibited by AM404. |
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AM404 is also a [[TRPV1]] agonist and inhibitor of [[cyclooxygenase]] COX-1 and COX-2, thus attenuating [[prostaglandin]] synthesis. AM404 is thought to induce its analgesic action through its activity on the [[endocannabinoid system|endocannabinoid]], [[COX]], and [[TRPV]] systems, all of which are present in [[Nociception|pain]] and [[thermoregulation|thermoregulatory]] pathways.<ref name="pmid15987694">{{cite journal | vauthors = Högestätt ED, Jönsson BA, Ermund A, Andersson DA, Björk H, Alexander JP, Cravatt BF, Basbaum AI, Zygmunt PM | display-authors = 6 | title = Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system | journal = The Journal of Biological Chemistry | volume = 280 | issue = 36 | pages = 31405–31412 | date = September 2005 | pmid = 15987694 | doi = 10.1074/jbc.M501489200 | s2cid = 10837155 | doi-access = free }}</ref> AM404 activates [[vanilloid receptor]]s causing [[vasodilation]] which is inhibited by the vanilloid receptor antagonist capsazepine.<ref>{{cite journal | vauthors = Zygmunt PM, Chuang H, Movahed P, Julius D, Högestätt ED | title = The anandamide transport inhibitor AM404 activates vanilloid receptors | journal = European Journal of Pharmacology | volume = 396 | issue = 1 | pages = 39–42 | date = May 2000 | pmid = 10822052 | doi = 10.1016/s0014-2999(00)00207-7 }}</ref> |
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The anticonvulsant action is mediated through [[Cannabinoid receptor type 1|CB1 receptors]].<ref name=":0" /> |
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== See also == |
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* [[VDM-11]] (2-methyl analogue) |
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== References == |
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{{Reflist}} |
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{{Cannabinoids}} |
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{{Analgesics}} |
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{{Cannabinoid receptor modulators}} |
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{{Prostanoid signaling modulators}} |
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{{Transient receptor potential channel modulators}} |
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[[Category:Anilides]] |
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[[Category:Phenols]] |
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[[Category:AM cannabinoids]] |
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[[Category:Fatty acid amides]] |
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[[Category:Human drug metabolites]] |
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[[Category:Endocannabinoid reuptake inhibitors]] |
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[[Category:Arachidonyl compounds]] |