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-HT_1c 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.

Reference:

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