Ws. Edgemond et al., THE BINDING OF NOVEL PHENOLIC DERIVATIVES OF ANANDAMIDE TO BRAIN CANNABINOID RECEPTORS, Prostaglandins, leukotrienes and essential fatty acids, 52(2-3), 1995, pp. 83-86
Arachidonylethanolamide (N-2-hydroxyethyl-arachidonamide) or 'anandami
de' is a naturally occurring derivative of arachidonic acid that has b
een shown to bind and activate cannabinoid receptors in the brain, Sin
ce 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 bin
ding affinity for the cannabinoid receptor. Two novel congeners of ana
ndamide containing aromatic hydroxyl groups were synthesized: N-2-(4-h
ydroxyphenyl)ethyl arachidonamide (HEA) and N-2-hydroxyphenyl arachido
namide (HPA). The affinity of these congeners for the brain cannabinoi
d receptor was determined by competition with [H-3]CP55940. HEA compet
ed for [H-3]CP55940 binding with a K-i of 600 nM; HPA had a K-i of 220
0 nM. These results indicate that increased size in the amide portion
of anandamide decreases affinity for the receptor, Phenylmethylsulfony
l flouride (PMSF), an inhibitor of anandamide catabolism by brain memb
ranes, had no effect on the binding of either HEA or HPA, We conclude
that these congeners are not substrates for the amidase that cataboliz
es anandamide.