SCH 23390, a Potential Benzazepine Antipsychotic with Unique Interactions on Dopaminergic Systems

SCH 23390 [R+)-8-chIoro-2,3,4,5-tetrahydro-3-methyI-5-phe-nyl-1 H-3-benzazepine-7-ol) possesses pharmacologic effects similar to standard antipsychotics, including selective supression of conditioned avoidance responding in rats and squirrel mon-keys, blockade of apomorphine-induced stereotypy in rats and blockade of methamphetamine-induced lethality in aggregated mice. At effective doses in these tests, no changes in gross behavior, neurological or autonomic function were observed. In contrast to the standards tested, SCH 23390 blocked dopamine-stimulated adenylate cyclase at concentrations (lCso 0.01 M) about 2000 times lower than those needed to block spiperone binding (ICso 24 SM). This suggests specific D1-receptor an-tagonism. Inability of SCH 23390 to cause hyperprolactinemia, considered to be a D-receptor effect, is consistent with thi