Cerebrodiene, arachidonyl-ethanolamide, and hybrid structures: potential for interaction with brain cannabinoid receptors.
Cerebrodiene (cis-9, 10-octadecenoamide) was recently isolated from cerebral fluid of sleep-deprived cats and shown to induce sleep in rats. Because this lipid amide is related to arachidonylethanolamide (AEA), and because AEA binds to the cannabinoid receptor with high affinity, we investigated the binding affinity of cerebrodiene and some analogs to the cannabinoid receptor. In addition, we tested the ability of these compounds to act as cannabinoid receptor agonists by determining GTP gamma S binding. Each of the analogs competed for [3H] CP55940 binding, but with relatively low affinity (Ki = 26-44 microM). These analogs were not able to stimulate binding of GTP gamma S at concentrations of 100 microM or 1 mM. We conclude that the sleep-inducing actions of cerebrodiene are not mediated via activation of the cannabinoid receptor.
Boring
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Division of Antiviral Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857, USA.
Berglund
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BA
Howlett
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AC
D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D051381:Rats; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*; D012890:Sleep / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C089587:cerebrodiene; D013110:Sphingosine; C078814:anandamide