Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.
Devane
W A
WA
Department of Natural Products, Medical Faculty, Hebrew University, Jerusalem, Israel.
Hanus
L
L
Breuer
A
A
Pertwee
R G
RG
Stevenson
L A
LA
Griffin
G
G
Gibson
D
D
Mandelbaum
A
A
Etinger
A
A
Mechoulam
R
R
D000577:Amides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002186:Cannabinoids / Q000378:metabolism; D002855:Chromatography, Thin Layer; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*; D013552:Swine
D000577:Amides; D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C078815:HU 243; C078814:anandamide