DOPr inverse agonists and systems in which inverse activity has been evidenced
| Type of System | DOR Species | Cell Type | Assay | Drug | Observations | Reference |
|---|---|---|---|---|---|---|
| Native systems | mDOR | NG108-15 hybrid cell | GTPase assay (membranes, high K) | ICI 174864, naloxone, ICI 154129 | Inhibition of basal activity ICI 174864 > ICI 154129 > NLX | Costa and Herz (1989) |
| GTPase assay (intact cells) | ICI 174866 | Inhibition of basal activity | ||||
| Binding affinity ± PTX (membranes) | ICI 174866 | Increased affinity (presence PTX) | ||||
| GTPγS binding (membranes) | ICI 174864 | Inhibition of basal activity | Szekeres and Traynor (1997) | |||
| NTI, BNTX, TIPP, NTB | No effect on basal activity | |||||
| Overexpression systems | mDOR | Rat 1 fibroblasts | GTPase assays (membranes) | ICI 174864 | Inhibition of basal activity | Mullaney et al. (1996) |
| HEK293 cells | Naloxone | No effect on basal activity | ||||
| ICI 174864 | Inhibition of basal activity of WT DOPr, D128N, and D128A; not Y129A | Befort et al. (1999) | ||||
| HEK293 cells | cAMP accumulation (intact cells) | ICI 174866 | Potentiation of cAMP, production by FSK | Chiu et al. (1996) | ||
| Naloxone, NTI | No effect on FSK stimulated cAMP production | |||||
| Rat DOR | C6 glioma | GTPγS binding absence Na+ ions (membranes) | ICI 174864, clocinnamox (C-CAM), BNTX, NTB | Inhibition of basal activity NTB ≥ BNTX ≥ C-CAM ≥ ICI 174864 | Neilan et al. (1999) | |
| Naloxone, NTI | No effect on basal activity | |||||
| Binding affinity ± Na+/GppNHp | ICI 174864, C-CAM | Leftward shift with Na+/GppNHp | ||||
| BNTX, NTB | No effect of Na+/GppNHp | |||||
| hDOR | HEK-293 cells | GTPγS binding (membranes) | TICP[Ψ] | Inhibition of basal activity of WT DOPr and of constitutively active DOPr (M262T) | Tryoen-Tóth et al. (2005) | |
| TICP[Ψ] | No effect on basal activity of WT DOPr, Inhibition of basal activity of constitutively active DOPr (M262T) | |||||
| Naloxone, NTB, BNTX, ICI 174864, H-Dmt-Tic-OH N,N(CH3)2-Dmt-Tic-NH2 | No effect on basal activity of WT DOPr or constitutively active DOPr (M262T) | |||||
| Reporter gene assay (intact cells) | N,N(CH3)2-Dmt-Tic-NH2 | Inhibition of basal activity of WT DOPr and constitutively active DOPr (M262T) | ||||
| Naloxone, NTB, BNTX | No effect on basal activity of WT DOPr, Inhibition of basal activity of constitutively active DOPr (M262T) | |||||
| GTPγS binding (membranes) | ICI 174864, N,N(CH3)2-Dmt-Tic-NH2, NTI | Inhibition of basal activity ICI 174864 ≥ N,N(CH3)2-Dmt-Tic-NH2 >>> NTI | Labarre et al. (2000) | |||
| GTPγS binding (membranes) | ICI 174864, TICP[Ψ], naloxone | Inhibition of basal activity TICP[Ψ] ≥ ICI 174864 ≥ NLX | Piñeyro et al. (2005), Audet et al. (2008) | |||
| cAMP accumulation | ICI 174864, TICP[Ψ] | Inhibition of basal activity TICP[Ψ] ≥ ICI 174864 | ||||
| hDOR | CHO cells | GTPγS binding (membranes) | ICI 174864, (2S,3R)TMT-l-Tic-OH | Inhibition of basal activity TMT-l-Tic-OH compound is more potent than ICI 174864 | Hosohata et al. (1999) | |
| ICI 174864, 17-fluoroethyl NTI derivatives | Inhibition of basal activity ICI 174864 > 17-fluoroethyl NTI derivatives | Nemoto et al. (2015) | ||||
| GH3 cells | GTPγS binding (membranes) | ICI 174864 | Inhibition of basal activity | Liu and Prather (2002), Martin et al. (2002) | ||
| TIPP, naltriben, naloxone, ICI 154129 | No effect on basal activity | |||||
| Binding affinity ± Na+/GppNHp | ICI 174864 TIPP | Leftward shift of affinity for ICI 174864 and TIPP, ICI 174864 > TIPP | ||||
| cAMP accumulation (intact cells) | ICI 174864 TIPP | ICI 174864 inhibits basal activity TIPP stimulates basal activity |
FSK, forskolin ICI 174866, N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH; NLX, naloxone; WT, wild type.