Revised Pharmacophore Model for 5-HT_2A Receptor Antagonists Derived from the Atypical Antipsychotic Agent Risperidone.

ABSTRACT: Pharmacophore models for 5-HT_2A receptor antagonists consist of two aromatic/hydrophobic regions at a given distance from a basic amine. We have previously shown that both aromatic/hydrophobic moieties are unnecessary for binding or antagonist action. Here, we deconstructed the 5-HT_2A receptor antagonist/serotonin-dopamine antipsychotic agent risperidone into smaller structural segments that were tested for 5-HT_2A receptor affinity and function. We show, again, that the entire risperidone structure is unnecessary for retention of affinity or antagonist action. Replacement of the 6-fluoro-3-(4-piperidinyl)-1,2-benz[ d]isoxazole moiety by isosteric tryptamines resulted in retention of affinity and antagonist action. Additionally, 3-(4-piperidinyl)-1,2-benz[ d

SUBMITTER: Shah UH 

PROVIDER: S-EPMC12746070 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature