Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7)

[Image: see text] 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-HT...

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Autores principales: Grattan, Vincent, Vaino, Andrew R., Prensky, Zachary, Hixon, Mark S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714530/
https://www.ncbi.nlm.nih.gov/pubmed/31497735
http://dx.doi.org/10.1021/acsomega.9b02144
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author Grattan, Vincent
Vaino, Andrew R.
Prensky, Zachary
Hixon, Mark S.
author_facet Grattan, Vincent
Vaino, Andrew R.
Prensky, Zachary
Hixon, Mark S.
author_sort Grattan, Vincent
collection PubMed
description [Image: see text] 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-HT(7) 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-HT(7) receptor has greater than 50-fold preference for the R enantiomer.
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spelling pubmed-67145302019-09-06 Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7) Grattan, Vincent Vaino, Andrew R. Prensky, Zachary Hixon, Mark S. ACS Omega [Image: see text] 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-HT(7) 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-HT(7) receptor has greater than 50-fold preference for the R enantiomer. American Chemical Society 2019-08-15 /pmc/articles/PMC6714530/ /pubmed/31497735 http://dx.doi.org/10.1021/acsomega.9b02144 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Grattan, Vincent
Vaino, Andrew R.
Prensky, Zachary
Hixon, Mark S.
Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7)
title Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7)
title_full Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7)
title_fullStr Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7)
title_full_unstemmed Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7)
title_short Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D(2) and D(3), while R Enantiomers Engage 5-HT(7)
title_sort antipsychotic benzamides amisulpride and lb-102 display polypharmacy as racemates, s enantiomers engage receptors d(2) and d(3), while r enantiomers engage 5-ht(7)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714530/
https://www.ncbi.nlm.nih.gov/pubmed/31497735
http://dx.doi.org/10.1021/acsomega.9b02144
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