GPR88 agonist 2 (compound 53) is a potent, brain-penetrant agonist of GPR88, with an EC50 of 14 µM in the GPR88 cAMP functional assay [1].

GPR88 agonist 2 significantly enhanced [35S] GTPγS binding activity (EC50: 8.9 μM) in the striatal membranes of WT mice but exhibited no activity in the striatal membranes of GPR88 KO mice [1].

GPR88 agonist 2, administered via intraperitoneal injection at a concentration of 20 mg/ml, demonstrated favorable plasma exposure (Cmax: 1670 ng/mL) and acceptable metabolic stability (T1/2: 4.66h, CL: 21 mL/mg/kg). This compound also exhibited adequate brain penetration (Cmax: 576 ng/mL). Pharmacokinetic analysis in mice at a dose of 20 mg/kg, intraperitoneally, revealed a Cmax of 1670 ng/mL in plasma with a half-life of 5.6 hours, a clearance rate of 21 mL/min/kg, and a brain-to-plasma ratio of 0.34, while in the brain, a Cmax of 576 ng/mL was observed.