Serotonergic component of SCH 23390: in vitro and in vivo binding analyses

A series of benzazepines related to SCH 23390 were tested for binding to the 5HT-2 receptor. The compounds tested inhibited the binding of 3H-ketanserin with K/sub I/ values generally greater than those for the D-1 receptor, but less than those for the D-2 receptor. When this serotonergic activity was correlated to the D-1 activity, the resulting coefficient was 0.84, indicating a strong correlation between the two activities. Conversely, the 5HT-2 activity did not show a good correlation with the D-2 activity. To further test the significance of the 5HT-2 binding of the SCH 23390, in vivo binding studies were performed using 125I-SCH 38840 in the frontal cortex, an area containing both D-1 and 5HT-2 receptors. The in vivo binding of 125I-SCH 38840 to frontal cortex exhibited peak levels one hour following subcutaneous administration, similar to the time course previously observed in striatum. The binding was both D-1 and tissue specific. Competition studies with selected standards demonstrated that inhibition of the binding to the frontal cortex, in contrast to the inhibition observed in the striatum, exhibited a Hill coefficient less than unity, implying interaction at more than one receptor subtype