PG01037

PG01037 is a highly selective small molecule antagonist of the dopamine D3 receptor, with approximately 133-fold selectivity for D3 over D2 receptors (Ki values: D3 = 0.7 nM, D2 = 93.3 nM, D4 = 375 nM). It acts at both the G-protein dependent and independent pathways of the D3 receptor. Preclinical studies show that it attenuates abnormal involuntary movements associated with L-DOPA in models of Parkinson’s disease and reduces drug-seeking behaviors in models of methamphetamine and cocaine addiction. PG01037 does not have significant effects on D2 or D4, and exerts inhibitory effects on methamphetamine-enhanced brain stimulation reward and cue-induced reinstatement of drug-seeking. It has been used primarily as a research tool to explore treatment modalities for substance use disorders, particularly for methamphetamine addiction, and is not approved for clinical use.