Table 2.

Pharmacological characterization of morphinan monovalent and bivalent ligands at the kappa opioid receptor using the [³⁵S]GTPγS binding assay

Compound	Structure	Kappa (AgonMCL-692, MCL-693, ist)		Kappa (Antagonist)
		EC50 (nM)	Emax (% maximal stimulation over basal)	IC50 (nM)	Imax (% maximal inhibition)
MCL-691 8		2.8 ± 0.90	90 ± 3.6	22 ± 3.7	37 ± 3.0
MCL-692 9b		2.4 ± 0.57	83 ± 0.95	17 ± 2.9	43 ± 4.3
MCL-693 13b		2.1 ± 0.076	90 ± 6.2	6.4 ± 2.7	30 ± 4.7
MCL-694 15c		18 ± 4.5	80 ± 4.8	7.7 ± 3.3	33 ± 3.8
MCL-695 15b		0.84 ± 0.089	100 ± 0.95	3.7 ± 1.2	23 ± 2.9
MCL-696 15a		12 ± 4.9	74 ± 16	49 ± 13	35 ± 2.2
MCL-715 11		5.5 ± 0.31	130 ± 3.3	NIa	NIa
MCL-714 12		7.3 ± 0.81	130 ± 12	NIa	NIa

Membranes from CHO cells that expressed the human κ opioid receptor were incubated with 12 concentrations of the compound in the presence of 0.08 nM [³⁵S]GTPγS for 60 min at 30°C. Nonspecific binding was measured by the inclusion of 10 μM GTPγS. For the inhibition experiments, [³⁵S]GTPγS binding was stimulated by the addition of 100 nM U50,488. Data are the mean ± SEM from three experiments performed in triplicate.

^aNI = No Inhibition