SCH23390

SCH23390 is a potent, selective antagonist of dopamine D1-like receptors, most notably the D1 receptor, with additional activity at the D5 subtype and some affinity for other targets at higher concentrations. It is widely used in neuroscience research to block D1 receptor–mediated signaling and to distinguish D1 effects from those of D2-family dopamine receptors.

Mechanism of action and pharmacology

SCH23390 acts as a competitive antagonist at D1-like receptors. By blocking D1 receptor signaling, it reduces adenylyl cyclase activation and downstream cAMP production in cells expressing these receptors. Its high affinity for D1 receptors makes it a common tool for dissecting the role of D1 signaling in various physiological and behavioral processes. At higher concentrations, it can interact with other receptor systems, such as 5-HT2 receptors, contributing to off-target effects in some experimental contexts.

Applications in research

SCH23390 is used in both in vivo and in vitro settings. In animals, it is employed to study the contribution of D1 receptor activity to locomotor responses, reinforcement learning, attention, and working memory tasks that engage prefrontal and striatal circuits. In brain slices and cultured systems, it blocks D1 receptor–mediated modulation of synaptic transmission and plasticity, helping to parse receptor-specific mechanisms.

Administration and safety

In research, SCH23390 is typically administered systemically (for example, intraperitoneally) or delivered directly into brain regions via microinjection. It readily crosses the blood–brain barrier, but dosing must be carefully controlled to avoid non-specific effects. SCH23390 is a research chemical and is not approved for clinical use in humans; at high doses, it can produce motor and other side effects in animal models due to off-target actions.

Note: This article summarizes its role as a research tool in dopamine D1 receptor pharmacology.