Table 1.

Receptor Binding Affinities and Functional Bioactivities of Compounds 1-9

		receptor affinitya (nM)		selectivity	functional bioactivity
Comp.	Structure	Kiδ	Kiμ	Kiμ/Kiδ	MVD pA2c	GPI IC50 (nM)b
	H-Dmt-Tic-NH2d	1.22	277	227	7.2	>10000
1	H-Dmt-Tic-ε-Lys(Z)-NH-CH2-Ph	0.53±0.08 (4)	3.15±0.39 (4)	5.9	8.27	1451±200
2	H-Dmt-Tic-ε-Lys(Ac)-NH-CH2-Ph	0.21±0.01 (3)	3.43±0.54 (4)	16.3	8.07	1990±674
3	H-Dmt-Tic-ε-Lys-NH-CH2-Ph	1.00±0.02 (4)	0.60±0.11 (4)	1.7*	7.81	553±173
4	H-Dmt-Tic-ε-Lys(Z)-NH-Ph	0.47±0.04 (4)	2.67±0.41 (4)	5.7	8.23	711±194
5	H-Dmt-Tic-ε-Lys(Ac)-NH-Ph	0.22±0.005 (3)	2.57±0.34 (4)	11.7	8.18	486±63
6	H-Dmt-Tic-ε-Lys-NH-Ph	2.02±0.20 (4)	0.89±0.12 (4)	2.3*	7.92	515±73
7	H-Dmt-Tic-NH-(CH2)4-CH(NH-Z)-Bid	0.86±0.06 (3)	2.78±0.27 (4)	3.2	7.82	618±140
8	H-Dmt-Tic-NH-(CH2)4-CH(NH-Ac)-Bid	0.21±0.01 (3)	0.99±0.06 (4)	4.7	8.12	610±185
9	H-Dmt-Tic-NH-(CH2)4-CH(NH2)-Bid	2.64±0.18 (3)	1.02±0.08 (3)	2.6*	8.09	434±26

^aThe K_i values (nM) were determined according to Cheng and Prusoff.²⁴ The mean ± SE with n repetitions in parenthesis is based on independent duplicate binding assays with five to eight peptide doses using several different synaptosomal preparations.

^bAgonist activity was expressed as IC₅₀ obtained from dose-response curves. These values represent the mean ± SE for at least five to six fresh tissue samples. Deltorphin II and endomorphin-2 were the internal standards for MVD (δ-opioid receptor bioactivity) and GPI (μ-opioid receptor bioactivity) tissue preparation, respectively.

^cThe pA₂ values of opioid antagonists against the agonist deltorphin II were determined by the method of Kosterlitz and Watt.²⁵

^dData taken from Salvadori et al.¹

^*μ-opioid receptor selectivity K_iδ/K_iμ.