TABLE 5

Operational model parameters for the functional interaction between Org27569 and cannabinoid agonists

pKA (cannabinoid equilibrium dissociation constant) and pKB (Org27569 equilibrium dissociation constant) were fixed to values determined in binding assays. Logα (binding cooperativity) was fixed to 0 to reflect the near neutral cooperativity between Org27569 and cannabinoid agonists. Log τB was fixed to –1000 to reflect the lack of Org27569 efficacy in these assays. Values represent the mean ± S.E.M. from at least three experiments performed in triplicate.

LigandLogβa [β]LogτAb [τA]
pERK1/2cAMPpERK1/2cAMP
CP55940>–10 [∼0]−1.0 ± 0.5 [0.1]0.3 ± 0.1 [2.0]0.3 ± 0.4 [2.0]
HU-210−1.0 ± 0.1 [0.1]>–10 [∼0]c0.3 ± 0.0 [2.0]0.7 ± 0.8 [5.0]
WIN55,212-2−0.6 ± 0.2 [0.3]>–10 [∼0]c0.4 ± 0.3 [2.5]0.3 ± 0.1 [2.0]
Δ9-THC−0.1 ± 0.0 [0.8]>–10 [∼0]c0.1 ± 0.1 [1.3]0.1 ± 0.8 [1.3]
Methanandamide−0.1 ± 0.1 [0.8]>–10 [∼0]c0.8 ± 0.0 [6.3]0.4 ± 0.2 [2.5]
Anandamide−0.1 ± 0.1 [0.8]>–10 [∼0]c0.8 ± 0.1 [6.3]0.9 ± 0.3 [7.9]
2-AG−0.4 ± 0.1 [0.4]>–10 [∼0]c0.0 ± 0.2 [1.0]0.2 ± 0.2 [1.6]
  • a Logarithm of the activation cooperativity factor between Org27569 and cannabinoid agonists.

  • b Logarithm of the functional efficacy.

  • c Logβ was allowed to float in the analysis, but could not be determined owing to the very high negative cooperativity.