RTI-13951-33 is a potent, selective, and brain-penetrant GPR88 agonist, with an EC 50 of 25 nM in GPR88 cAMP functional assay. RTI-13951-33 elevates [ 35 S]-GTPγS binding (EC 50, 535 nM) in mouse striatal membranes however not in membranes from GPR88 KO mice [1]. RTI-13951-33 has weak affinities at kappa opioid receptor (KOR; K i, 2.29 μM), vesicular monoamine transporter (VMAT; K i, 4.23 μM), and moderate affinity at serotonin transporter (SERT; K i, 0.75 μM) but RTI-13951-33 poorly inhibits SERT (IC 50, 25.1±2.7 μM) [1].

RTI-13951-33 (10 and 20 mg/kg, i.p.) decreases alcohol lever responses in a rat model of alcohol self-administration in a dose-dependent manner [1]. RTI-13951-33 (10 mg/kg, i.p.) shows sufficient brain penetration, with t 1/2 of 48 min and 87 min in rat plasma and brain [1].