TABLE 1

AM6538, AM4112, and AM6542 are competitive antagonists of hCB1

Inhibition of forskolin-stimulated cAMP accumulation in 3xHA-hCB1 Chinese hamster ovary (CHO) cells cotreated with forskolin (cAMP assays only) and hCB1 agonists and antagonists for 30 minutes and βarrestin2 recruitment in hCB1 DiscoveRx CHO cells cotreated with hCB1 agonists and antagonist for 90 minutes. Data are presented as mean with 95% confidence interval. For antagonism of cAMP inhibition: n = 5 (THC with AM4112, THC with AM6542), n = 3 for all other treatments. For antagonism of β arrestin 2 recruitment, n = 4 (JWH-018 with AM6542), n = 3 for all other treatments; experiments performed in duplicate. Data were fit to a competitive nonlinear regression model using Prism 6.0. Concentration-response curves are available in Supplemental Figs. S1S3. pA2 values for inhibition of forskolin-stimulated cAMP accumulation with THC excluded 1 and 10 µM AM4112 and AM6542 in global nonlinear regression analysis.

Antagonist pA2 values for inhibition of forskolin-stimulated cAMP accumulation by hCB1 agonists.
AntagonistCP55,940THCJWH-018
 SR141716A9.5 (9.3–9.9)a9.2 (8.7–9.8)a8.6 (7.3–9.8)
 AM65389.0 (8.6–9.2)a9.4 (9.1–9.9)a8.1 (5.8–11)
 AM41128.7 (5.5–12)9.2 (8.7–9.6)9.3 (9.0–9.7)
 AM65428.2 (7.2–9.2)8.2 (6.7–9.6)8.8 (8.1–9.6)
Antagonist pA2 values for β arrestin 2 recruitment by hCD1 agonists.
AntagonistCP55,940THCJWH-018
 SR141716A9.5 (9.3–9.9)a8.7 (6.2–11)a7.8 (7.5–8.0)
 AM65389.4 (9.1–9.6)a7.8 (7.1–8.8)a7.8 (7.6–8.0)
 AM41128.6 (7.1–9.9)8.8 (6.5–11)8.4 (7.3–9.5)
 AM65429.1 (8.5–9.6)8.9 (6.5–11)8.2 (7.3–9.1)
  • a Data are from Hua et al. (2016) wherein SR141716A and AM6538 are originally described as competitive antagonists of CP55,940 and THC.