TABLE 4

Binding parameters for the allosteric interaction between Org27569 and cannabinoid agonists determined in binding interaction experiments

Data were fitted to an allosteric ternary complex model (eq. 3) to determine the cooperativity between Org27569 and cannabinoid agonists (Logα′). The binding cooperativity between [3H]SR141716A and Org27569 (Logα) was highly negative (>–10) and could not be defined owing to complete inhibition of [3H]SR141716A binding by Org27569. The negative logarithm of the radioligand dissociation constant was fixed to that determined from homologous competition binding experiments (pKA 8.5). Values represent the mean ± S.E.M. from at least three experiments performed in triplicate.

LigandLogαa [α′]pKBbpKicBmaxd
CP559400.5 ± 1.0 [3.2]5.4 ± 0.16.8 ± 0.6391 ± 11.1
HU-2100.0 ± 0.7 [1.0]5.6 ± 0.17.0 ± 0.3393 ± 15.3
WIN55,212-20.6 ± 0.5 [4.0]5.2 ± 0.15.8 ± 0.2427 ± 16.8
Δ9-THC0.3 ± 0.2 [2.0]5.6 ± 0.16.7 ± 0.1393 ± 16.2
Methanandamide0.3 ± 0.6 [2.0]5.4 ± 0.15.5 ± 0.2405 ± 12.4
Anandamide0.3 ± 0.4 [2.0]5.4 ± 0.05.2 ± 0.1411 ± 8.02
2-AG0.5 ± 0.2 [3.2]5.4 ± 0.15.9 ± 0.6399 ± 9.88
  • a Logarithm of the binding cooperativity factor between Org27569 and cannabinoid agonists.

  • b The negative logarithm of the allosteric modulator dissociation constant.

  • c The negative logarithm of the competing orthosteric ligand dissociation constant.

  • d The maximum number of [3H]SR141716A binding sites expressed as percentage of specific binding.