RESEARCH & RELATED - OTHER PROJECT INFORMATION - PROJECT SUMMARY/ABSTRACT This Core B facility will serve as a technical and scientific support unit for the three Projects (1, 2, 3) of this Program Project Grant. Its major goals involve: (1) the re-synthesis and scale-up of compounds in sufficient quantities to address the in vitro and in vivo needs of the research laboratories involved in the projects; (2) the testing of all new orthosteric ligands for their affinities for the CB1 and CB2 cannabinoid receptors; (3) the testing of orthosteric ligands for their abilities to bind irreversibly/tightly to CB1 and CB2; (4) determining the functional properties of ligands initially in the cAMP assay (both orthosteric and allosteric); (5) the testing of anandamide analogs for their abilities to act as substrates of the endocannabinoid deactivating enzyme, FAAH; (6) determining the metabolic and plasma stabilities of ligands using liver microsomal and plasma preparations, respectively; (7) screening for off-target interactions against a broad panel of G protein-coupled receptors, ion channels, transport proteins as well as endocannabinoid metabolizing enzymes; and (8) evaluation of a select group of novel ligands in mice for their bioavailability in CNS and plasma; the top candidates of each class in an extensive pharmacokinetic profiling. Compounds produced under the auspices of Core B will also be made available to other laboratories identified in this Program Project whose collaboration is at no cost to the grant.