A-381393

A-381393 (CAS No.: 726174-00-1) is a potent, selective, and brain-penetrant dopamine D4 receptor antagonist widely utilized as a pharmacological tool in neuropharmacology and receptor signaling research. It exhibits high affinity for human dopamine D4 receptor variants (D4.2, D4.4, and D4.7) in the low nanomolar range, with marked selectivity exceeding several thousand-fold over other dopamine receptor subtypes, including D1, D2, D3, and D5, and displays moderate affinity for the serotonin 5-HT2A receptor. Functionally, A-381393 effectively inhibits agonist-induced GTP-γ-S binding and dopamine-stimulated intracellular calcium flux in cells expressing the D4 receptor, while showing negligible activity in D2L- or D3-expressing systems, underscoring its subtype specificity. In addition, it suppresses downstream signaling events associated with D4 receptor activation, including c-Fos expression and ERK1/2 phosphorylation, indicating its utility in probing intracellular signaling cascades linked to dopaminergic neurotransmission. This compound is commonly applied in in vitro cell-based assays and in vivo experimental models to investigate the physiological and molecular roles of D4 receptor signaling in the central nervous system, as well as in the screening and characterization of novel dopaminergic ligands, with experimental concentrations or dosing regimens varying according to specific study designs.