Novel, highly potent, selective 5-HT2A/D2 receptor antagonists as potential atypical antipsychotics.

Abstract The discovery of N -substituted-pyridoindolines and their binding affinities at the 5-HT 2A , 5-HT 2C and D 2 receptors, and in vivo efficacy as 5-HT 2A antagonists is described. The structure–activity relationship of a series of core tetracyclic derivatives with varying butyrophenone sidechains is also discussed. This study has led to the identification of potent, orally bioavailable 5-HT 2A /D 2 receptor dual antagonists as potential atypical antipsychotics.