Fig. 2: Differential agonist and inverse agonist activities of the antipsychotic drugs at the G protein pathways and for recruitment of β-arrestins.

a Concentration response curves depicting the inverse agonist activities of risperidone, clozapine, olanzapine and haloperidol using the ebBRET-based EMTA biosensors in HEK293 cells heterologously expressing the untagged 5-HT_2AR, the biosensor (rGFP-CAAX along with p63-RlucII for the Gα_q family and Rap1GAP-RlucII for Gα_i1/z) and the respective Gα subunits. b Heatmap illustrating the potency (logEC₅₀) of inverse agonist activity shown by risperidone, clozapine, olanzapine and haloperidol from the concentration response curves. The empty cell with a cross indicates no inverse agonist activity. c Concentration response curves depicting the partial agonist activities of aripiprazole and cariprazine at the Gα_q family using the ebBRET-based EMTA biosensors in HEK293 cells heterologously expressing the untagged 5-HT_2AR, the biosensor (rGFP-CAAX along with p63-RlucII for the Gα_q family). d Curves of the six antipsychotic drugs at pathways where there was no activation when tested in the agonist mode using the ebBRET-based EMTA biosensors in HEK293 cells overexpressing the untagged 5-HT_2AR, the biosensors (rGFP-CAAX along with p63-RlucII for the Gα_q family, Rap1GAP-RlucII for Gα_i/o/z family, β-arrestin-RlucII/WT-GRK2 for β-arrestins) and the respective Gα subunits (for Gα_q and Gα_i/o/z families). Results are expressed as ΔBRET (ligand-promoted BRET) (mean ± SEM; n = 3).