In vivo binding to dopamine receptors: a correlate of potential antipsychotic activity.

Antagonists of dopamine receptors (especially those of the D2 subtype) have long been recognized as effective antipsychotics. SCH 39166, a dopamine D1 selective antagonist, is now also being evaluated for its clinical antipsychotic properties. The studies described herein determine the binding affinity of a variety of dopamine receptor antagonists (both dopamine D1 and D2 selective compounds) for the dopamine D1 and D2 receptors, in vivo, and correlate this affinity with their behavioral activity in the rat conditioned avoidance response (CAR) test. The in vivo binding affinities of the D1 selective compounds at the dopamine D1 site exhibited a high correlation (r = 0.97) with their activities in the rat CAR test. Likewise, D2 selective compounds' inhibition of in vivo binding to dopamine D2 receptors correlated with their behavioral potencies (r = 0.98). Conversely, any binding of selective agents to their non-targeted receptor did not correlate with their behavioral activity. These data suggest that in vivo binding to either dopamine D1 and/or D2 receptors is predictive of potential antipsychotic efficacy.