Figure 3.

Pharmacological profiles of aporphine ligands. (A–C) Radiolabeled ligand binding curves for 5-HT_2C, 5-HT_2B, and 5-HT_2A in the presence of aporphines or lorcaserin. See also Table S4 for K_i values. (D–F) G_q-mediated calcium mobilization induced by 1857, 15781, and lorcaserin. 1857 and 15781 displayed partial agonism only at 5-HT_2C while lorcaserin activated three 5-HT₂ receptors. (G) β-arrestin2 recruitment stimulated by 1857, lorcaserin, and ergotamine (ERG, a known β-arrestin2 biased agonist for 5-HT_2C). 1857 has no measurable agonist activity following ERG treatment. (H) SFSR summary of aporphines discovered in this study. N-unsubstituted aporphine 1857 and 15781 act as selective 5-HT_2C agonists. 1857 also displays G_q bias with no measurable β-arrestin activity. N-methyl substituted aporphine 14148 and 15856 act as nonselective 5-HT₂ antagonists. NA, not assayed. Data represent means ± SEM of three independent experiments performed in triplicate.