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 D1-like receptor antagonist with a K(i) of 0.2 and 0.3 nM for the D1 and D5
dopamine receptor subtypes, respectively. 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. 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 D1-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 D1 receptors facilitates seizure activity, whereas activation of D2 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 D1 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 D1 receptor, in neurological function and dysfunction.