TABLE 3

Biased agonism by cannabinoids (KA predetermined from radioligand binding assays)

LogR (τ/KA), ΔLogRτ/KA), ΔΔLogR (ΔΔτ/KA) ratios and bias factors for cannabinoid ligands, relative to 2-AG, at the CB1R were obtained by fitting the data to an operational model of agonism (eq. 5), where KA was fixed to that predetermined in radioligand binding assays. Values represent the mean ± S.E.M. from at least four independent experiments carried out in triplicate.

LigandcAMPpERK1/2cAMP/pERK1/2
LogRΔLogRLogRΔLogRΔΔLogRBF
CP559408.3 ± 0.22.6 ± 0.27.9 ± 0.12.0 ± 0.10.6 ± 0.23.8
HU-2108.8 ± 0.23.1 ± 0.27.6 ± 0.11.8 ± 0.11.3 ± 0.2*20.7
WIN55,212-26.9 ± 0.21.2 ± 0.26.8 ± 0.11.0 ± 0.10.2 ± 0.21.6
Δ9-THC7.1 ± 0.21.4 ± 0.26.4 ± 0.10.6 ± 0.10.8 ± 0.26.0
Methanandamide6.9 ± 0.21.2 ± 0.25.8 ± 0.1−0.1 ± 0.11.3 ± 0.2*18.2
Anandamide6.2 ± 0.20.6 ± 0.25.8 ± 0.1−0.1 ± 0.10.8 ± 0.24.5
2-AG5.7 ± 0.20.0 ± 0.25.9 ± 0.10.0 ± 0.10.0 ± 0.21.0
  • * P < 0.05, one-way analysis of variance with Bonferroni’s multiple comparison test between ΔΔLogR for 2-AG compared with other cannabinoids.