Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D₂ and D₃, while R Enantiomers Engage 5-HT₇.

ABSTRACT: Benzamide antipsychotics such as amisulpride are dosed as racemates though efficacy is assumed to be mediated through S enantiomer binding to D₂ 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 D₂ 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.

SUBMITTER: Grattan V 

PROVIDER: S-EPMC6714530 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature