Evaluation of Functional Selectivity of Haloperidol, Clozapine, and LASSBio-579, an Experimental Compound With Antipsychotic-Like Actions in Rodents, at G Protein and Arrestin Signaling Downstream of the Dopamine D₂ Receptor.

ABSTRACT: LASSBio-579, an N-phenylpiperazine antipsychotic lead compound, has been previously reported as a D₂ receptor (D₂R) ligand with antipsychotic-like activities in rodent models of schizophrenia. In order to better understand the molecular mechanism of action of LASSBio-579 and of its main metabolite, LQFM 037, we decided to address the hypothesis of functional selectivity at the D₂R. HEK-293T cells transiently coexpressing the human long isoform of D₂ receptor (D₂LR) and bioluminescence resonance energy transfer (BRET)-based biosensors were used. The antagonist activity was evaluated using different concentrations of the compounds in the presence of a submaximal concentration of dopamine (DA), after 5 and 20 min. For both signalin

SUBMITTER: Silva RR 

PROVIDER: S-EPMC6558205 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature