2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Chemistry*
  • Cannabinoid Receptor Modulators
  • Cannabinoids / isolation & purification
  • Cannabinoids / pharmacology
  • Female
  • Gastrointestinal Motility / drug effects
  • Glycerides / isolation & purification*
  • Glycerides / pharmacology
  • Hypothermia / chemically induced
  • Mice
  • Models, Animal
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / metabolism
  • Swine


  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Glycerides
  • Receptors, Cannabinoid
  • Receptors, Drug
  • noladin ether