Table 1.

Summary of the in vitro activity of the O-2093 and its four novel analogs

Compound	[14C]AEA uptake by RBL-2H3 cells (IC50, μM)	[14C]AEA hydrolysis by RBL-2H3 cell membranes (IC50, μM)	rCB1 (Ki, μM)	hCB2 (Ki, μM)	[Ca2+]i in HEK cells expressing hTRPV1 (max. effect at 10  μM, as % of the effect of 4  μMionomycin)
O-2093	17.3±2.0	>50	1.29±0.11	2.38±0.51	27.1±2.6*
O-3246	1.4±0.2	>50	2.69±0.19	2.18±0.38	18.2±1.4*
O-3262	2.8±0.3	>50	2.02±0.02	1.31±0.12	24.4±2.2*
O-2247	43.3±4.1	>50	>10	8.04±0.80	16.7±1.8
O-2248	>50	27.9±3.4	>10	5.12±0.21	8.1±1.1
OMDM-2	4.1±0.8	>50	5.10±0.30	4.95±1.40	31.0±3.2*

Data are reported as IC₅₀ (μM) for the uptake and hydrolysis assays, K_i (μM) for the binding assays, and as maximal effect (i.e. as % of the effect on calcium observed with 4 μM ionomycin), for the [Ca²⁺]_i assay, and are means±s.e.m. of 3 experiments. Asterisk denotes compounds that were tested in this assay also in the presence of 20 nM of the TRPV1 antagonist capsazepine, with no change in the effect observed. The previously reported (Ortar et al., 2003; de Lago et al., 2004) inhibitor of AEA uptake, OMDM-2, was used as reference compound.