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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-9-24
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pubmed:abstractText |
Arachidonoyl-serotonin inhibits in a mixed-type manner the metabolism of the endocannabinoid anandamide by the enzyme fatty acid amidohydrolase. In the present study, compounds related to arachidonoyl-serotonin have been synthesised and investigated for their ability to inhibit anandamide hydrolysis by this enzyme in rat brain homogenates. Removal of the 5-hydroxy from the serotonin head group of arachidonoyl-serotonin produced a compound (N-arachidonoyltryptamine) that was a 2.3-fold weaker inhibitor of anandamide hydrolysis, but which also produced its inhibition by a mixed-type manner (Ki(slope) 1.3 microM; Ki(intercept) 44 microM). Replacement of the amide linkage in this compound by an ester group further reduced the potency. In contrast, replacement of the arachidonoyl side chain by a linolenoyl side chain did not affect the observed potency. N-(Fur-3-ylmethyl) arachidonamide (UCM707), N-(fur-3-ylmethyl)linolenamide and N-(fur-3-ylmethyl)oleamide inhibited anandamide hydrolysis with pI50 values of 4.53, 5.36 and 5.25, respectively. The linolenamide derivative was also found to be a mixed-type inhibitor. It is concluded that the 5-hydroxy group of arachidonoyl-serotonin contributes to, but is not essential for, inhibitory potency at fatty acid amidohydrolase.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amidohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Endocannabinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Polyunsaturated Alkamides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cannabinoid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/anandamide,
http://linkedlifedata.com/resource/pubmed/chemical/arachidonoylserotonin,
http://linkedlifedata.com/resource/pubmed/chemical/fatty-acid amide hydrolase
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1475-6366
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
225-31
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pubmed:dateRevised |
2007-3-21
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pubmed:meshHeading |
pubmed-meshheading:14506913-Amidohydrolases,
pubmed-meshheading:14506913-Animals,
pubmed-meshheading:14506913-Arachidonic Acids,
pubmed-meshheading:14506913-Binding Sites,
pubmed-meshheading:14506913-Brain,
pubmed-meshheading:14506913-Dose-Response Relationship, Drug,
pubmed-meshheading:14506913-Endocannabinoids,
pubmed-meshheading:14506913-Enzyme Inhibitors,
pubmed-meshheading:14506913-Hydrolysis,
pubmed-meshheading:14506913-Inhibitory Concentration 50,
pubmed-meshheading:14506913-Kinetics,
pubmed-meshheading:14506913-Models, Chemical,
pubmed-meshheading:14506913-Polyunsaturated Alkamides,
pubmed-meshheading:14506913-Rats,
pubmed-meshheading:14506913-Receptors, Cannabinoid,
pubmed-meshheading:14506913-Receptors, Drug,
pubmed-meshheading:14506913-Serotonin
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pubmed:year |
2003
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pubmed:articleTitle |
Inhibition of fatty acid amidohydrolase, the enzyme responsible for the metabolism of the endocannabinoid anandamide, by analogues of arachidonoyl-serotonin.
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pubmed:affiliation |
Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden. cf@pharm.umu.se
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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