Evaluation of the effects of the enantiomers of reduced haloperidol, azaperol, and related 4-amino-1-arylbutanols on dopamine and .sigma. receptors

The enantiomers of reduced haloperidol (3a), azaperol (3b), and the related compound BMY-14802 (3c) were prepared in high optical purity. The affinity of these compounds for dopamine D2 and D3 receptors, and σ S1 and S2 sites was determined in vitro. Both enantiomers of 3a display greatly decreased affinity for D2 and D3 receptors compared to haloperidol, although they still possess affinities in the 100-200-nM range. Both enantiomers of 3a possess potent and equal affinity for S1 sites (K i :1-2 nM), only slightly weaker than haloperidol (K i :0.33 nM). At S2 sites, (R)-(+)-3a displays similar affinity to haloperidol (K i :31 and 26 nM, respectively), while (S)-(-)-3a is slight more potent (K i :8.2 nM)