RT Journal Article SR Electronic T1 Characterization of a Novel Endocannabinoid, Virodhamine, with Antagonist Activity at the CB1 Receptor JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1020 OP 1024 DO 10.1124/jpet.301.3.1020 VO 301 IS 3 A1 Amy C. Porter A1 John-Michael Sauer A1 Michael D. Knierman A1 Gerald W. Becker A1 Michael J. Berna A1 Jingqi Bao A1 George G. Nomikos A1 Petra Carter A1 Frank P. Bymaster A1 Andrea Baker Leese A1 Christian C. Felder YR 2002 UL http://jpet.aspetjournals.org/content/301/3/1020.abstract AB The first endocannabinoid, anandamide, was discovered in 1992. Since then, two other endocannabinoid agonists have been identified, 2-arachidonyl glycerol and, more recently, noladin ether. Here, we report the identification and pharmacological characterization of a novel endocannabinoid, virodhamine, with antagonist properties at the CB1 cannabinoid receptor. Virodhamine is arachidonic acid and ethanolamine joined by an ester linkage. Concentrations of virodhamine measured by liquid chromatography atmospheric pressure chemical ionization-tandem mass spectrometry in rat brain and human hippocampus were similar to anandamide. In peripheral tissues that express the CB2 cannabinoid receptor, virodhamine concentrations were 2- to 9-fold higher than anandamide. In contrast to previously described endocannabinoids, virodhamine was a partial agonist with in vivo antagonist activity at the CB1 receptor. However, at the CB2 receptor, virodhamine acted as a full agonist. Transport of [14C]anandamide by RBL-2H3 cells was inhibited by virodhamine. Virodhamine produced hypothermia in the mouse and acted as an antagonist in the presence of anandamide both in vivo and in vitro. As a potential endogenous antagonist at the CB1 receptor, virodhamine adds a new form of regulation to the endocannabinoid system. The American Society for Pharmacology and Experimental Therapeutics