TABLE 1

MOR functional and binding specificity for TRV130

Potencies and efficacies were determined for the indicated MOR species orthologs. Efficacy values are calculated as percent of maximal response to morphine (h,r,m,d MOR), U69,593 (hKOR), and DPDPE (hDOR) (n > 10 independent experiments performed in duplicate) except dMOR (n = 3). K_i _high and K_{i low} represent the high- and low-affinity binding component, respectively (n = 2–5 independent determinations).

TRV130	cAMP				β-Arrestin-2				[³H]Diprenorphine
TRV130	pEC₅₀	S.D.	EC₅₀	Efficacy (%)	pEC₅₀	S.D.	EC₅₀	Efficacy (%)	K_{i high}	K_{i low}
			nM				nM		nM	nM
hMOR	8.1	0.04	7.9	83	7.4	0.22	40.0	14	6 ± 1.7	551 ± 263
mMOR	9.4	0.06	0.4	104	7.9	0.06	12.6	74	1 ± 0.3	39 ± 21
rMOR	8.4	0.03	4.0	90			N.Q.		18 ± 3.7	203 ± 26
dMOR	8.3	0.01	5.0	92	8.0	0.02	9.4	24	N.D.
hNOP	6.4	0.09	398	58			N.Q.		N.D.
hKOR	5.8	0.03	1585	58			N.Q.		>10,000
hDOR	5.5	0.04	3162	46			N.Q.		N.D.

d, dog; h, human; m, mouse; N.D., not determined; N.Q., not quantifiable; r, rat.