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The rank order of potencies for SCRA stimulation of cAMP (Gαs ) was PB-22 5F-MDMB-PICA JWH-018 ≈ AB-FUBINACA XLR-11. By contrast, the potency of SCRAs for inhibition of cAMP (Gαi/o ) was 5F-MDMB-PICA AB-FUBINACA PB-22 JWH-018 XLR-11. The different rank order of potency and EMax of the SCRAs to stimulate Gαs -like signaling compared to Gαi/o signaling suggests differences in G protein preference between SCRAs. Understanding the apparent differences among these drugs may contribute to unravelling their c

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