TABLE 1

Potency for opioid agonist stimulation of adenylate cyclase inhibition, induction of internalization, and receptor desensitization in MOR1-expressing HEK293 cells For EC50 calculation, μ-opioid receptor-expressing HEK293 cells were incubated with increasing amounts of agonists (10-13-10-4 M), and adenylate cyclase inhibition and internalization data were analyzed (sigmoidal dose-response curve fit analysis; GraphPad Software Inc., San Diego, CA). RAVE was defined as relative activity versus endocytosis. Similar to Whistler et al. (1999), the peptide DAMGO was defined as having activity and endocytosis of 1 and thus a RAVE of 1. Based on the DAMGO values, morphine has a relative activity of 0.98 and relative endocytosis of 0.1, resulting in a RAVE of 9.8.

Agonist Endocytosis AC Inhibition RAVE EC50 Desensitization
AC Inhibition Endocytosis Ratio
% nM nM %
Morphine 5 ± 2 64 ± 5 9.8 25 ± 4 >1 mM >40,000 65 ± 4
Buprenorphine 7 ± 2 31 ± 7 3.36 36 ± 3 >1 mM >27,777 69 ± 5
Hydromorphone 7 ± 2 54 ± 4 5.93 84 ± 4 >1 mM >11,905 55 ± 8
Pethidine 5 ± 1 62 ± 6 9.5 280 ± 30 >1 mM >3571 53 ± 4
Oxycodone 9 ± 5 59 ± 7 5 290 ± 22 >1 mM >3448 46 ± 3
Nortilidine 6 ± 3 63 ± 8 8.1 370 ± 41 >1 mM >2702 42 ± 5
Fentanyl 22 ± 6 44 ± 5 1.54 129 ± 53 80,000 ± 10,000 620 41 ± 5
Methadone 25 ± 3 57 ± 13 1.76 11 ± 6 10,000 ± 2300 909 43 ± 4
Piritramide 30 ± 6 60 ± 8 1.54 21 ± 8 1800 ± 700 86 34 ± 4
β-Endorphin 32 ± 5 56 ± 5 1.35 13.7 ± 2.5 1000 ± 269 73 30 ± 4
DAMGO 50 ± 5 65 ± 7 1 13 ± 3 600 ± 123 46 25 ± 3
Sufentanil 48 ± 7 70 ± 7 1.12 0.055 ± 0.03 0.9 ± 0.32 16.4 15 ± 2
Etonitazene 47 ± 4 72 ± 3 1.18 1.9 ± 0.6 0.7 ± 0.35 0.37 10 ± 4