Medical College of Wisconsin
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The binding of novel phenolic derivatives of anandamide to brain cannabinoid receptors. Prostaglandins Leukot Essent Fatty Acids 1995 Feb-Mar;52(2-3):83-6 PMID: 7784462

Pubmed ID

7784462

Abstract

Arachidonylethanolamide (N-2-hydroxyethyl-arachidonamide) or 'anandamide' is a naturally occurring derivative of arachidonic acid that has been shown to bind and activate cannabinoid receptors in the brain. Since other potent ligands for the cannabinoid receptor have an aromatic hydroxyl group, we investigated the hypothesis that replacement of the ethanolamine hydroxyl with an aromatic hydroxyl will increase the binding affinity for the cannabinoid receptor. Two novel congeners of anandamide containing aromatic hydroxyl groups were synthesized: N-2-(4-hydroxyphenyl)ethyl arachidonamide (HEA) and N-2-hydroxyphenyl arachidonamide (HPA). The affinity of these congeners for the brain cannabinoid receptor was determined by competition with [3H]CP55940. HEA competed for [3H]CP55940 binding with a Ki of 600 nM; HPA had a Ki of 2200 nM. These results indicate that increased size in the amide portion of anandamide decreases affinity for the receptor. Phenylmethylsulfonyl fluoride (PMSF), an inhibitor of anandamide catabolism by brain membranes, had no effect on the binding of either HEA or HPA. We conclude that these congeners are not substrates for the amidase that catabolizes anandamide.

Author List

Edgemond WS, Campbell WB, Hillard CJ

Authors

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-0028800749   27 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acids
Binding, Competitive
Cell Membrane
Endocannabinoids
In Vitro Techniques
Male
Phenylmethylsulfonyl Fluoride
Polyunsaturated Alkamides
Rats
Rats, Sprague-Dawley
Receptors, Cannabinoid
Receptors, Drug
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e