RTI-13951-33 hydrochloride

RTI-13951-33 hydrochloride is a potent, selective, and brain-penetrant GPR88 agonist, with an EC₅₀ of 25 nM in GPR88 cAMP functional assay. RTI-13951-33 hydrochloride reduces alcohol reinforcement and intake behaviors in rats^[1]. IC50 & Target: EC50: 25 nM (GPR88)^[1] In Vitro: RTI-13951-33 is a potent, selective, and brain-penetrant GPR88 agonist, with an EC₅₀ of 25 nM in GPR88 cAMP functional assay. RTI-13951-33 elevates [³⁵S]-GTPγS binding (EC₅₀, 535 nM) in mouse striatal membranes but 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), however, RTI-13951-33 poorly inhibits SERT (IC₅₀, 25.1±2.7 μM)^[1]. In Vivo: RTI-13951-33 (10 and 20 mg/kg, i.p.) dose-dependently decreases alcohol lever responses in a rat model of alcohol self-administration^[1].
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^[1].