. Author manuscript; available in PMC: 2008 Jun 23.

Published in final edited form as: J Med Chem. 2006 Sep 7;49(18):5640–5643. doi: 10.1021/jm0605785

Table 2.

Functional Activity at the μ, δ and κ Receptors^a

	[³⁵S]GTP-γ-S binding (Agonism)
	μ		δ		κ
	EC₅₀ (nM)	E_max (%)	EC₅₀ (nM)	E_max (%)	EC₅₀ (nM)	E_max (%)
MCL 101^b	1.6±0.2	50±2.5	NT	NT	1.3±0.44	80±6.8
MCL 450	8.9±0.76	79±2.3	2.8±0.75	18±1.7	6.0±1.0	130±5.1
MCL 451	NT	NT	NT	NT	NA	0.95±2.2

	[³⁵S]GTP-γ-S binding (Agonism)
	μ		δ		κ
	IC₅₀ (nM)	I_max (%)	IC₅₀ (nM)	I_max (%)	IC₅₀ (nM)	I_max (%)
MCL 101^b	20±3	50±3	NT	NT	NT	NT
MCL 450	97±21	47±1.7	3.9±0.34	84±5.2	No Inhibition	No Inhibition
MCL 451	NT	NT	10±1.5	93±1.0	NT	NT

Membranes from CHO that stably expressed only the μ, δ, or κ receptor were incubated with various concentrations of the compounds. The stimulation of [³⁵S]GTPγS binding was measured as described in the Experimental Section. The E_max value is the maximal percent stimulation obtained with the compound. The EC₅₀ value is the concentration of compound needed to produce 50% of the E_max value. When the E_max value was 30% or lower, it was not possible to calculate an EC₅₀ value. To determine the antagonistic properties of a compound, membranes were incubated with 100 nM of the κ agonist U50,488 or 200 nM of the μ agonist DAMGO or 100 nM of the δ agonist SNC-80 in the presence of varying concentration of the compound. The I_max value is the maximal percent inhibition obtained with the compound. The IC₅₀ value is the concentration of compound needed to produce half-maximal inhibition. NT, Not Tested; NA, Not Active.

Data from Peng, X. et al. J. Med. Chem. 2006, 49g , 256-262.