RTI-13951-33

EC50: 25 nM (GPR88)

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 but not in membranes from GPR88 KO mice.
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), however, RTI-13951-33 poorly inhibits SERT (IC ₅₀ , 25.1 ± 2.7 μM).

RTI-13951-33 (10 mg/kg, i.p.) has sufficient brain penetration, with t _1/2 of 48 min and 87 min in rat plasma and brain.
RTI-13951-33 (10 and 20 mg/kg, i.p.) dose-dependently decreases alcohol lever responses in a rat model of alcohol self-administration.