Antipsychotic Benzamides Amisulpride And Lb-102 Display Polypharmacy As Racemates, S Enantiomers Engage Receptors D-2 And D-3, While R Enantiomers Engage 5-Ht7

Benzamide antipsychotics such as amisulpride are dosed as racemates though efficacy is assumed to be mediated through S enantiomer binding to D-2 receptors. At prescribed doses, the benzamides likely display polypharmacy since brain exposure should be sufficient to engage the 5-HT7 receptors, as well. Curiously, the studies herein reveal that racemic dosing is required to engage both targets since the D-2 receptor has an almost 40-fold selectivity for the S enantiomer, while the 5-HT7 receptor has greater than 50-fold preference for the R enantiomer.