TABLE 1

Allosteric TCM binding parameters for various modulators at mouse brain CB1 receptors pKB is the negative logarithm of the equilibrium dissociation constant for the allosteric modulator at the free receptor, determined using nonlinear regression according to eq. 2 under Materials and Methods. Values represent the mean ± S.E.M. of four to eight experiments. For these analyses, the negative logarithm of the KA value (eq. 2) was fixed to nine for each radioligand, based on previous saturation binding assays. Log α is the logarithm of the cooperativity factor. α is the antilogarithm (geometric mean) of the cooperativity factor with range in parentheses, based on the estimated log α values.

Radioligand & Parameter Allosteric Modulator
Org 27569 Org 27759 Org 29647
[3H]CP 55,940
   pKB 5.67 ± 0.23 6.31 ± 0.32 5.78 ± 0.26
   Log α 1.14 ± 0.17 0.47 ± 0.10 0.44 ± 0.07
   α 14 (9.3–20.4) 3 (2.3–3.7) 2.8 (2.3–3.2)
[3H]SR 141617A
   pKB 5.95 ± 0.14 6.21 ± 0.14 5.84 ± 0.18
   Log α –1.04 ± 0.25 –0.48 ± 0.10 –0.44 ± 0.16
   α 0.09 (0.05–0.16) 0.33 (0.26–0.42) 0.36 (0.25–0.52)