in rats: To assess the activation of central CB1 receptors evoked by treatment with A-836339 at a higher dose, phMRI was employed to visualize regional changes in cerebral blood volume. phMRI experiments: rats were divided into seven treatment groups, where each group received either vehicle (5% dimethyl sulfoxide/polyethylene glycol 400 i.v.), A-836339 (at 3 or 10 μmol/kg i.v.), SR141716A (13 μmol/kg i.p.), AM630 (6 μmol/kg i.p.), A-836339 (10 μmol/kg i.v.) plus SR141716A (13 μmol/kg i.p.), or A-836339 (10 μmol/kg i.v.) plus AM630 (6 μmol/kg i.p.). In the groups where animals received A-836339 along with SR141716A or AM630, animals were pretreated with SR141716A or AM630 approximately 40 min before the infusion of A-836339. A high dose of A-836339 (10 μmol/kg i.v.) produced a CNS activation pattern consistent with that of A-834735, a previously characterized, nonselective agonist that activates the CB1 receptor. A lower dose of A-836339 (3 μmol/kg i.v.) did not produce a significant CNS activation pattern.

The affinities of A-836339 at cannabinoid receptors were determined by the displacement of radioligand [3H]CP 55,940 in competition binding assays using membranes prepared from recombinant HEK cells stably expressing the CB1 or CB2 receptor from human and rat. A-836339 exhibited high potencies at both human and rat CB2 receptors, with Ki values of 0.64 and 0.76 nM, respectively.