Table 1.
In vitro pharmacological profile of CE-178253
| Competition Binding Assays | GTPγ[35S] Functional Assay (human CB1 in CHO cells) | |||||||
|---|---|---|---|---|---|---|---|---|
| Ki (nM) ± SEM (n) | Antagonist | Inverse Agonist | ||||||
| Compound | Rat brain | hCB1 | hCB2 | Selectivity | Ki (nM) | IC50 (nM) | Intrinsic Activity | Slope |
| CE-178253 | 0.43 ± 0.13 (5) | 0.33 ± 0.07 (5) | 15666 ± 6173 (3) | > 30,000 | 0.07 ± 0.01 (5) | 2 ± 0.56 (3) | 21% | 0.83 |
| SR141716A | 0.6 ± 0.1 (32) | 1.0 ± 0.1 (73) | 285 ± 27 (6) | 285 | 0.54 ± 0.2 (25) | 3 ± 1 (2) | 30% | 1 |
| CP-55940 | 4.2 ± 0.6 (7) | 2.9 ± 1.1 (10) | 2.0 ± 0.1 (95) | 1.5 | Agonist | ND | ND | ND |
ND, Not determined
The pharmacological properties of CE-178253, SR141716A and CP-55940 were assessed at human CB1, human CB2 receptors and rat brain membranes (predominantly CB1). The intrinsic activity assessed in inverse agonist assay is the percent decrease in basal GTPγ[35S] binding.