SCH 23390: The First Selective Dopamine D1‐Like Receptor Antagonist

Abstract

SCH 23390, the halobenzazepine (R)‐(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H–3‐benzazepine, is a highly potent and selective dopamine D 1‐like receptor antagonist with a Ki of 0.2 and 0.3 nM for the D 1 and D 5 dopamine receptor subtypes, respectively.In vitro, it also binds with high affinity to the 5‐HT 2 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 D 1‐mediated response. Previous in vivo pharmacological studies with SCH 23390 have shown it to abolish generalized seizures evoked by the chemoconvulsants: pilocarpine and soman. These studies provide evidence of the potential importance of D 1‐like dopaminergic receptor mechanisms in facilitating the initiation and spread of seizures. The inference from a majority of studies is that the activation of dopamine D 1 receptors facilitates seizure activity, whereas activation of D 2 receptors may inhibit the development of seizures. SCH 23390 has also been used in studies of other neurological disorders in which the dopamine system has been implicated, such as psychosis and Parkinson's disease. Apart from the study of neurological disorders, SCH 23390 has been extensively used as a tool in the topographical determination of brain D 1 receptors in rodents, nonhuman primates, and humans. In summary, SCH 23390 has been a major tool in gaining a better understanding of the role of the dopamine system, more specifically the D 1 receptor, in neurological function and dysfunction.