TABLE 2

Dissociation rate constants for [3H]CP 55,940 at mouse brain CB1 receptors in the absence or presence of allosteric modulators Parameter values were estimated using global nonlinear regression analysis, with the minimal plateau value constrained to 0. An extra-sum-of-squares (F test) revealed that all data sets were adequately fitted assuming common values for the percentage of the slowly dissociating state (Span1, 59.03 ± 3.03%) and the fast dissociating state (Span2, 35.75 ± 2.97%). k1 (slow) and k2 (fast) are the dissociation rate constants for the slow and fast dissociating states, respectively.

k1 (slow) Half-Life Slow k2 (fast) Half-Life Fast
× 10–2 min–1 min min–1 min
Vehicle 1.40 ± 0.08 49.4 (55.6–44.5) 0.294 ± 0.037 2.35 (3.14–1.88)
Org 27569 (100 nM) 0.79 ± 0.03** 87.8 (94.2–82.2) 0.091 ± 0.006** 7.59 (8.69–6.74)
Org 27569 (1 μM) 0.36 ± 0.03** 194 (235–165) 0.056 ± 0.005** 12.43 (15.31–10.44)
Org 27759 (1 μM) 0.64 ± 0.03** 108 (119–99) 0.099 ± 0.008** 7.03 (8.29–6.11)
Org 27759 (10 μM) 0.28 ± 0.03** 249 (304–210) 0.042 ± 0.004** 16.36 (19.6–14.03)
Org 29647 (1 μM) 0.98 ± 0.04** 71.0 (76.5–66.2) 0.344 ± 0.026 2.01 (2.36–1.75)
Org 29647 (10 μM) 0.26 ± 0.004** 264 (369–205) 0.036 ± 0.005** 19.53 (26.01–15.64)
  • ** P < 0.01, one-way analysis of variance followed by Dunnett's post test