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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
1996-12-10
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pubmed:abstractText |
Several analogs of an endogenous cannabimimetic, arachidonylethanolamide (anandamide), were synthesized to study the structural requirements of the ethanolamide head group. CB1 receptor affinities of the analogs were evaluated by a standard receptor binding assay using tritiated CP-55,940 as the radioligand and compared to anandamide which was shown to have a Ki of 78 nM. Replacement of the amide carbonyl oxygen by a sulfur atom had a detrimental effect on the CB1 affinity. The thio analogs of both anandamide and (R)-methanandamide showed very weak affinity for CB1. The secondary nature of the amidic nitrogen was also shown to be important for affinity, indicating a possible hydrogen-bonding interaction between the amide NH and the receptor. Introduction of a phenolic moiety in the head group resulted in the loss of receptor affinity except when a methylene spacer was introduced between the amidic nitrogen and the phenol. A select group of analogs were also tested for their affinity for the CB2 receptor using a mouse spleen preparation and were found to possess low affinities for the CB2 sites. Notably, anandamide and (R)-methanandamide demonstrated high selectivity for the CB1 receptor. Overall, the data presented here show that structural requirements of the head group of anandamide are rather stringent.
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pubmed:grant |
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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/3-(2-hydroxy-4-(1,1-dimethylheptyl)p...,
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Cnr2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclohexanols,
http://linkedlifedata.com/resource/pubmed/chemical/Polyunsaturated Alkamides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cannabinoid, CB2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cannabinoid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/anandamide
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4515-9
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pubmed:dateRevised |
2009-9-4
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pubmed:meshHeading |
pubmed-meshheading:8893848-Adjuvants, Immunologic,
pubmed-meshheading:8893848-Analgesics,
pubmed-meshheading:8893848-Animals,
pubmed-meshheading:8893848-Arachidonic Acids,
pubmed-meshheading:8893848-Brain,
pubmed-meshheading:8893848-Calcium Channel Blockers,
pubmed-meshheading:8893848-Cyclohexanols,
pubmed-meshheading:8893848-Kinetics,
pubmed-meshheading:8893848-Mice,
pubmed-meshheading:8893848-Polyunsaturated Alkamides,
pubmed-meshheading:8893848-Rats,
pubmed-meshheading:8893848-Receptor, Cannabinoid, CB2,
pubmed-meshheading:8893848-Receptors, Cannabinoid,
pubmed-meshheading:8893848-Receptors, Drug,
pubmed-meshheading:8893848-Structure-Activity Relationship
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pubmed:year |
1996
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pubmed:articleTitle |
Head group analogs of arachidonylethanolamide, the endogenous cannabinoid ligand.
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pubmed:affiliation |
Department of Pharmaceutical Sciences, University of Connecticut, Storrs 06269, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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