Quantitative in vitro and in vivo pharmacological profile of CE-178253, a potent and selective cannabinoid type 1 (CB1) Receptor Antagonist

Table 1 In vitro pharmacological profile of CE-178253

	Competition Binding Assays				GTPγ[³⁵S] Functional Assay (human CB₁ in CHO cells)
	K_i (nM) ± SEM (n)				Antagonist	Inverse Agonist
Compound	Rat brain	hCB₁	hCB₂	Selectivity	K_i (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.