Fig. 4: Pathway-specific antagonistic activity of the six antipsychotic drugs tested.
From: Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HT2A receptor
a-i Concentration response curves with the activity of the six antipsychotics tested in the antagonist mode (i.e; in the presence of an EC80 concentration of 5-HT) using the ebBRET-based EMTA biosensors in HEK293 cells heterologously expressing the untagged 5-HT2AR and the biosensor (rGFP-CAAX along with p63-RlucII for Gαq family, Rap1GAP-RlucII for Gαi/o/z, and the respective Gα subunits, as well as β-arrestin1-RlucII or β-arrestin2-RlucII and WT-GRK2 for recruitment of β-arrestins). Results are expressed as % response of 5-HT (EC80) at the respective pathways (normalized with respect to the response of 5-HT (EC80)) (mean ± SEM; n = 3–5). j Heatmap depicting the equilibrium dissociation constant (Kb) of the antipsychotics calculated based on the modified Cheng-Prusoff equation as described in the methods section along with the pKi values reported in the literature (a [66]; b [67]; c [68]; d [69]; e [70]; f [28]; g [56]; h [71]). The empty cells with a cross indicate no activity in the antagonist mode whereas cells colored blue indicate IC50 > 10 µM.
