SCH-23390, A POTENTIAL BENZAZEPINE ANTI-PSYCHOTIC WITH UNIQUE INTERACTIONS ON DOPAMINERGIC SYSTEMS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (2) , 462-468
Abstract
SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol] possesses pharmacologic effects similar to standard antipsychotics, including selective suppression of conditioned avoidance responding in rats and squirrel monkeys, 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 (IC50 [median inhibitory concentration] = 0.01 .mu.M) .apprx. 2000 times slower than those needed to block spiperone binding (IC50 = 24 .mu.M). This suggests specific D1-receptor antagonism. Inability of SCH 23390 to cause hyperprolactinemia, considered to be a D2-receptor effect, is consistent with this hypothesis. SCH 23390 showed lower increases in dopamine turnover suggesting that the blockade of SCH 23390 may be more specific for post- than presynaptic sites. Additional evidence for the selectivity of SCH 23390 among putative postsynaptic dopamine sites includes its lack of effect on apomorphine-induced hypothermia or emesis. SCH 23390 apparently is a selective D1-receptor antagonist.