Table 3.
Kappa Agonist Effects | EC50 (nM) ± S.E.M. | Emax (% stimulation) ± S.E.M. | Functional activity |
---|---|---|---|
Butorphan | 1.3 ± 0.44 | 80 ± 6.8 | Agonist |
9 | 2.8 ± 0.43 | 75 ± 1.1 | Agonist |
7a | 4.9 ± 0.82 | 58 ± 7.4 | Agonist |
10 | 0.85 ± 0.053 | 65 ± 0.68 | Agonist |
4a | 7.3 ± 1.6 | 54 ± 3.5 | Agonist |
4b | 6.4 ± 0.87 | 60 ± 8.0 | Agonist |
11 | 1.6 ± 0.23 | 86 ± 7.3 | Agonist |
Kappa Antagonist Effects | IC50 (nM) ± S.E.M. | Imax (% inhibition) ± S.E.M. | |
Butorphan | NT | NT | |
9 | No inhibition | No inhibition | |
7a | No inhibition | No inhibition | |
10 | No inhibition | No inhibition | |
4a | No inhibition | No inhibition | |
4b | No inhibition | No inhibition | |
11 | No inhibition | No inhibition |
To determine agonist effects, 12 different concentrations of the compounds were incubated with CHO cells that expressed the κ opioid receptor. Antagonist activity was determined by measuring the inhibition of [35S]GTPγS binding by the compounds. For antagonist studies, [35S]GTPγS binding was stimulated with 100 nM U50,488. The stimulation observed with U50,488 was set at 100% control binding.