Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev D E, Kustanovich I, Mechoulam R
Department of Medicinal Chemistry and Natural Products, Hebrew University Medical Faculty, Jerusalem 91120, Israel.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3662-5. doi: 10.1073/pnas.061029898. Epub 2001 Mar 20.
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).
迄今为止，已鉴定出两种内源性大麻素受体激动剂。它们是多不饱和脂肪酸的乙醇酰胺——花生四烯酸乙醇酰胺（阿南达米德）是酰胺系列中最知名的化合物——以及2-花生四烯酸甘油酯，它是酯系列中唯一已知的内源性大麻素。我们现在报告从猪脑中分离出的第三种醚型内源性大麻素2-花生四烯酰甘油醚（诺拉汀醚）的一个实例。诺拉汀醚的结构通过质谱和核磁共振光谱确定，并通过与合成样品比较得到证实。它与CB(1)大麻素受体结合（K(i)=21.2±0.5 nM），并在小鼠中引起镇静、体温过低、肠道蠕动停止和轻度抗伤害感受。它与CB(2)受体的结合较弱（K(i)>3 microM）。
