TABLE 1

Comparison of potency and maximum response of agonist-induced [³⁵S]GTPγS binding and arrestin-3 recruitment for 22 opioid agonists acting at MOPr in HEK293 cells

Agonists are positioned in the table according to potency in the [³⁵S]GTPγS binding assay, the most potent agonist (etorphine) being positioned at the top. Also shown are K_D values for the agonists as determined in [³H]naloxone competition binding experiments. Max Response columns indicate maximum [³⁵S]GTPγS response for each agonist expressed relative to that obtained for DAMGO (taken as 1) and maximum arrestin-3 recruitment response for each agonist expressed relative to alfentanil (taken as 1), respectively. Apart from the exceptions noted, values represent mean ± S.E.M. of at least three independent experiments for each agonist.

Agonist	[³⁵S]GTPγS Binding		Arrestin-3 Recruitment		K_D
Agonist	EC₅₀	Max Response	EC₅₀	Max Response	K_D
	nM		nM		nM
Etorphine	0.55 ± 0.16	0.92 ± 0.06	6.8 ± 1.0	1.22 ± 0.08	3.5 ± 0.3
Norbuprenorphine	1.7 ± 0.7	0.93 ± 0.02	84.6 ± 12.1	1.16 ± 0.09	24.6 ± 4.5
Met-enkephalin	7.7 ± 1.9	0.88 ± 0.06	939 ± 325	1.38 ± 0.16	281 ± 13
DAMGO	11.2 ± 1.93	1.04 ± 0.02	414 ± 90	1.24 ± 0.09	228 ± 74
Buprenorphine	14.5 ± 5.11	0.55 ± 0.04	—^{^a}	—	0.9 ± 0.1
Leu-enkephalin	30.9 ± 12.0	0.87 ± 0.05	5160 ± 1490	0.94 ± 0.10	744 ± 84
Levorphanol	33.1 ± 17.2	0.98 ± 0.11	265 ± 112	0.24 ± 0.03	23.2 ± 2.2
Fentanyl	56.8 ± 31.2	1.14 ± 0.11	210 ± 42	0.89 ± 0.13	158 ± 24
Pentazocine	77.9^{^b}	0.26^{^b}	—	—	149 ± 27
6MAM	73.3 ± 26.1	0.96 ± 0.03	1540 ± 700	0.45 ± 0.07	318 ± 86
M6G	81.0 ± 27.7	0.87 ± 0.06	1600 ± 370	0.27 ± 0.05	437 ± 227
Methadone	87.2 ± 42.2	1.18 ± 0.09	2110 ± 999	1.14 ± 0.16	552 ± 81
Alfentanil	90.3 ± 16.2	0.99 ± 0.01	638 ± 192	1.01 ± 0.16	866 ± 156
Morphine	97.5 ± 28.5	0.98 ± 0.03	322 ± 44	0.19 ± 0.03	250 ± 52
Endomorphin 2	138 ± 31	1.04 ± 0.04	311 ± 121	1.22 ± 0.01	283 ± 54
Endomorphin 1	183 ± 96	1.11 ± 0.11	226 ± 43	0.95 ± 0.04	281 ± 31
Normorphine	259 ± 165	1.11 ± 0.14	768 ± 165	0.52 ± 0.09	578 ± 141
Meptazinol	289^{^b}	0.38^{^b}	—	—	462 ± 71
Oxycodone	564 ± 195	0.95 ± 0.12	1460 ± 1290	0.18 ± 0.03	1550 ± 328
Meperidine	>10,000^{^c}	—	—	—	7110 ± 3300
Cyclazocine	>10,000^{^c}	—	—	—	17500 ± 725
Nalorphine	>10,000^{^c}	—	—	—	13.1 ± 0.6

6MAM, 6-monoacetylmorphine.
↵a It was not possible to determine values because maximum agonist response was not obtained or because of lack of significant response at highest agonist concentrations used.
↵b Values for these agonists determined from a curve fitted to the mean data, as it was not possible to obtain fits of individual curves.
↵c Estimation because maximum response was not obtained at the highest concentration of agonist used.