SCH-23390 is a Selective Dopamine D1-Like Receptor Antagonist

Dopamine Receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Abnormal dopamine receptor signaling and dopaminergic nerve function can lead to several neuropsychiatric disorders. Thus, dopamine receptors are common neurologic drug targets. There are at least five subtypes of dopamine receptors, D1, D2, D3, D4, and D5. At the minimum, mammalian D2-like receptors comprise the D2, D3, and D4 subtypes along with their multiple splice variants and polymorphic forms. And the D1-like subfamily includes the human D1 and D5 receptors.

The D1 and D5 receptors are postsynaptic receptors. D1 and D5 subtypes can mediate excitatory neurotransmission. Current evidence indicates that D1-like receptors exists in diverse species, including the fruit fly, cockroach, locust, spider, eel, earthworm, flatworm, goldfish, tree frog, lizard, chicken, rodent, monkey and humans. Dopamine D1-like receptors are intimately implicated in dopaminergic regulation of fundamental neurophysiologic processes such as mood, motivation, cognitive function, and motor activity. Both D1– and D5-deficient mice develop hypertension (AAP). Because the physiological functions of the D1-like receptors include vasorelaxation and inhibition of renal Na+ reabsorption.

SCH 23390 is a highly potent and selective dopamine D1-like receptor antagonist.

SCH-23390 is the first potent and selective dopamine D1-like receptor antagonist. SCH-23390 inhibits D1 and D5 receptor with nanomolar potency. In vitro, it also binds with high affinity to the 5-HT2 and 5-HT1c serotonin receptor subtypes. However, the doses required to induce a similar response in vivo are greater than 10-fold higher than those required to induce a D1-mediated response. SCH 23390 can abolish generalized seizures evoked by the chemoconvulsants: pilocarpine and soman. SCH 23390 is also effective in other neurological diseases related to the dopamine system, such as psychosis and Parkinson’s disease. In summary, SCH 23390 has been a major tool in gaining a better understanding of the role of the dopamine system, more specifically the D1 receptor, in neurological function and dysfunction.


[1]. Undieh AS. Pharmacol Ther. 2010 Oct;128(1):37-60.