2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor.
Two types of endogenous cannabinoid-receptor agonists have been identified thus far. They are the ethanolamides of polyunsaturated fatty acids--arachidonoyl ethanolamide (anandamide) is the best known compound in the amide series--and 2-arachidonoyl glycerol, the only known endocannabinoid in the ester series. We report now an example of a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), isolated from porcine brain. The structure of noladin ether was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by comparison with a synthetic sample. It binds to the CB(1) cannabinoid receptor (K(i) = 21.2 +/- 0.5 nM) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds weakly to the CB(2) receptor (K(i) > 3 microM).
Department of Medicinal Chemistry and Natural Products, Hebrew University Medical Faculty, Jerusalem 91120, Israel.
L
L
Hanus
S
S
Abu-Lafi
E
E
Fride
A
A
Breuer
Z
Z
Vogel
D E
DE
Shalev
I
I
Kustanovich
R
R
Mechoulam
D000818:Animals; D001923:Brain Chemistry; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000302:isolation & purification / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D005989:Glycerides / Q000302:isolation & purification* / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced; D051379:Mice; D023421:Models, Animal; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000378:metabolism; D013552:Swine
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D005989:Glycerides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C424442:noladin ether