Figure 1.
Structures of morphine, oxymorphone and N-substituted morphinans 1–6.
Ph, phenyl.
Table 1.
Opioid receptor binding affinities and selectivities at MOP, DOP and KOP receptors.
Figure 2.
In vitro agonist activities at the MOP receptor of morphine, oxymorphone and N-methylmorphinans 1, 4 and 6.
Concentration-response curves in (A) [35S]GTPγS functional assay with membranes from CHO expressing human MOP receptor and (B) calcium mobilization experiments performed with CHO cells co-expressing the human MOP receptor and the Gαqi5 protein. Activity is calculated as percentage of maximal stimulation produced by DAMGO. Data are shown as the mean ± SEM (n≥3).
Table 2.
In vitro agonist potency and efficacy.
Figure 3.
Time-course of antinociceptive effects produced by morphine, oxymorphone and N-methylmorphinans 1, 4 and 6.
The effect of morphine (1.25–5 mg/kg), oxymorphone (0.2–1 mg/kg), and compounds 1 (0.05–0.5 mg/kg), 4 (0.5–5 mg/kg), and 6 (0.1–0.5 mg/kg) in the hot-plate test (A, left panel) and in the tail-flick test (B, right panel). Hot-plate and tail-flick latencies (in seconds) were determined in mice before (0 min) and after s.c. drug administration (30, 60 and 120 min). Data are shown as the mean ± SEM (n = 5–6 mice per group).
Figure 4.
Dose-dependent antinociceptive effects produced by morphine, oxymorphone and N-methylmorphinans 1, 4 and 6.
(A) Hot-plate test. (B) Tail-flick test. Hot-plate and tail-flick latencies (as %MPE) are shown at 30 min (peak of action) after s.c. drug administration to mice. Data are shown as the mean ± SEM (n = 5–6 mice per group).
Table 3.
Antinociceptive activities.