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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

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

Grattan Vincent V Vaino Andrew R AR Prensky Zachary Z Hixon Mark S MS

ACS omega 20190815 9

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 <i ...[more]

PMID: 31497735

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