TABLE 2

EC50 and Emax values for CB2 ligands in the cyclase and arrestin assays

The EC50 values presented with 95% confidence intervals, while the Emax data are presented as mean ± S.E.M. and P values (*P < 0.05; **P < 0.01, ***P < 0.001). The P values were obtained use the Student’s t test and by comparing the efficacy of the test compound at 1 µM with the effect of 1 µM CP55940. For antagonists, the comparisons were to basal signaling. The *P and **P values represent compounds meeting >20% activation or inhibition thresholds (compared with CP55940); the ***P values represent compounds that failed to meet the 20% activation or inhibition thresholds (compared with CP55940).

CompoundCyclase AssayArrestin Recruitment Assay
EC5095% CIEmaxaP valueEC5095% CIEmaxP value
nMnM%nM
CP5594031.1–8.557 ± 0.5NA3.20.2–5.5100NA
THC7.32.3–20.452 ± 1.2*NANA3 ± 1.3***
L759633NANANANANANA10 ± 1.5***
L759656NANANANANANA11 ± 1.1***
JWH1332015.5–28.161 ± 1.1*NANA18 ± 2.1***
KM2331.60.2–7.750 ± 1.3**NANA17 ± 3.4***
HU3083027.6–35.160 ± 3.4NSNANA3 ± 1.6***
WIN55212-21610.5–21.740 ± 1.2**7.23.4–11.030 ± 1.2*
AM12412018.1–22.527 ± 5.2*NANA17 ± 1.9***
STS1355240.9–65.1131 ± 2.3*1.51–3.962 ± 1.1*
JWH0153024.4–38.123 ± 0.72*160101–22528 ± 1.5**
GW405833NANA0***NANA4 ± 2.6***
UR144NANA12 ± 0.79578.2–13570 ± 1.2**
MAM220171.1–11.526 ± 2.1*NANA12 ± 3.4***
AM22322217.3–24.324 ± 1.3*NANA15 ± 2.7***
AM2233NANA7 ± 1.6***NANA10 ± 1.5***
AM12481512.3–17.324 ± 3.1*7162.1–9952 ± 2.3*
A8363394339.2-4654 ± 1.1NS0.70.04–2.4100 (NS)NS
GP1a1410.1–25.251 ± 7.6NS179.1–27.338 ± 1.2*
AM1710115.5–15.648 ± 4.3NS41.6–7.191 ± 3.6NS
SER6014019.2–76.125 ± 1.1**NANANANA
4Q3CNANANANANANANANA
GW833972A2820–56.122 ± 7.5*9056.1–13588 ± 2.5**
2AG4.10.4–7.839 ± 0.7*NANANANA
Methanandamide2017.9–25.355 ± 0.5*NANANANA
4 MethylhonokiolNANANANA5142.1–6255 ± 4.6**
β Caryophyllene3022.1–36.65 ± 1.1***NANANANA
AM6302521.6–29.319 ± 2.4b**93.8–14.443 ± 4.2**
JTE9072214.1–24.58 ± 0.8b**0.10.01–3.647 ± 1.5**
SR144528NANA11 ± 0.7b**1511–18.343 ± 3.1c**
  • AM1241, (2-iodo-5-nitrophenyl)-(1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl)methanone; AM1248, 1-[(N-methylpiperidin-2-yl)methyl]-3-(adamant-1-oyl)indole; AM2232, (1-(4-cyanobutyl)-3-(naphthalen-1-oyl)indole); A836339, N-[3-(2-methoxyethyl)-4,5-dimethyl-1,3-thiazol-2-ylidene]-2,2,3,3-tetramethylcyclopropane-1-carboxamide; CI, confidence interval; Emax, maximal inhibition of forskolin-stimulated cAMP production; GP1a, N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-1,4-dihydro-6-methylindeno[1,2-c]pyrazole-3-carboxamide; GW833972A, 2-[(3-chlorophenyl)amino]-N-(4-pyridinylmethyl)-4-(trifluoromethyl)-5-pyrimidinecarboxamide hydrochloride; HU308, 4-[4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-methanol; JTE907, N-(1,3-benzodioxol-5-ylmethyl)-1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinolinecarboxamide; JWH015, (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone; JWH133, (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran; KM233, (−)-(6aR,7,10,10aR)-tetrahydro-6,6,9-trimethyl-3-(1-methyl-1-phenylethyl)-6H-dibenzo[b,d]pyran-1-ol; L759633, (6aR,10aR)-1-methoxy-6,6,9-trimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene; L759656, (6aR,10aR)-3-(1,1-dimethylheptyl)-6a,7,8,9,10,10a-hexahydro-1-methoxy-6,6-dimethyl-9-methylene-6H-dibenzo[b,d]pyran; MAM2201, [1-(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl)-methanone; NA, not applicable/cannot be determined (inhibition or activation <20% threshold); NS, non statistically significant difference; SER601, N-(Adamant-1-yl)-6-isopropyl-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxamide THC, tetrahydrocannabinol; 4Q3C, 1,​4-​dihydro-​8-​methoxy-​4-​oxo-​1-​pentyl-​N-​tricyclo[3.3.1.13,​7]dec-​1-​yl-​3-​quinolinecarboxamide; WIN55212-2, [(3R)-​2,​3-​dihydro-​5-​methyl-​3-​(4-​morpholinylmethyl)pyrrolo[1,​2,​3-​de]-​1,​4-​benzoxazin-​6-​yl]-​1-​naphthalenyl-​methanone,​ monomethanesulfonate.

  • a Percentage of inhibition of forskolin-stimulated cAMP production.

  • b Above basal.

  • c Below basal.