TABLE 1

Binding affinities and functional activities of SRI International compounds at NOP and opioid receptors compared with N/OFQ, buprenorphine, and morphine

Receptor binding and [35S]GTPγS binding was measured in Chinese hamster ovary cell membranes containing the appropriate human receptor, as described in Dooley et al. (1997). Binding constants are shown as Ki ± S.D. values for each compound, which are derived from at least two individual experiments conducted in triplicate. An EC50 value of >10,000 for [35S]GTPγS binding indicates no significant stimulation at that concentration.


Compound

NOP Receptor

μ-Opioid Receptor

κ-Opioid Receptor
Ki
EC50
% Stim
Ki
EC50
% Stim
Ki
EC50
% Stim
N/OFQ 0.2 ± 0.04 4.0 ± 0.1 100 133 ± 30.0 N.D. N.D. N.D. N.D.
Morphine N.D. N.D. 1.1 ± 0.0 15.6 ± 0.5 93 ± 2.8 46.9 ± 14.5 484 ± 213.0 62 ± 7.0
SR 16435a 7.49 ± 0.8 28.7 ± 0.6 45.0 ± 5 2.70 ± 0.0 29.5 ± 10.0 30 ± 0.0 31.74 ± 4.8 >10,000
SR 16430 6.49 ± 1.4 >10,000 60.95 ± 15.0 >10,000 219.47 ± 18.0 >10,000
Buprenorphine
77.42 ± 16.0
>10,000

1.5 ± 0.8
24.9 ± 14.0
17.7 ± 0.4
1.5 ± 0.2
>10,000

  • % Stim, % stimulation; N.D., not determined.

  • a Taken from Zaveri et al. (2004).