Table 2.
Evidence for physiological effect of ligands targeting MOP-DOP receptor heteromers
| Ligand | Experimental model | Outcome | References |
|---|---|---|---|
| Morphine | Tail-immersion test (acute treatment) | Antinociception (i.m.) Morphine antinociception (ED50 of 2.67 mg/kg) is lowered by pretreatment with 3.2 mg/kg of naltrindole (ED50 of 15.48 mg/kg). | Yekkirala et al., 2012 |
| Fentanyl | Tail-immersion test (acute treatment) | Antinociception (i.m.) Fentanyl antinociception (ED50 of 0.011 mg/kg) is lowered by pretreatment with 3.2 mg/kg of naltrindole (ED50 of 0.048 mg/kg). | Yekkirala et al., 2012 |
| Methadone | Tail-immersion test (acute treatment) | Antinociception (i.m.) Methadone antinociception (ED50 of 1.79 mg/kg) is lowered by pretreatment with 3.2 mg/kg of naltrindole (ED50 of 4.35 mg/kg). | Yekkirala et al., 2012 |
| SNC80 | Tail-flick test (acute treatment) | Antinociception (i.t.) SNC80 antinociception (ED50 of ∼50 nmol) is lowered in the MOP receptor and DOP receptor knockout mice (ED50 of 131 nmol and 327 nmol, respectively). | Metcalf et al., 2012 |
| Bivalent ligand (MDAN) | Tail-flick test (acute treatment) | Antinociception (s.c., i.c.v., and i.t.) MDAN21 exhibits 100 times more potent antinociception (i.c.v., ED50 of 0.04 nmol) than morphine (i.c.v., ED50 of 4.1 nmol) without development of tolerance or dependence. | Daniels et al., 2005 |
| Biased agonist (CYM51010) | Tail-flick test (acute treatment) | CYM51010 (s.c.) exhibits equipotent antinociception to morphine with lesser antinociceptive tolerance. | Gomes et al., 2013b |
| TAT-fused peptide (MOP receptor TM1–TAT) | Tail-flick test (chronic morphine treatment) | Disruption of MOP-DOP receptor interaction by TAT-fused peptide increases morphine antinociception and decreases the development of antinociceptive tolerance. | He et al., 2011 |
| TAT-fused peptide (DOP receptor carboxyl tail–TAT) | Forced swim test Novelty-induced hypophagia Elevated plus maze | Disruption of MOP-DOP receptor interaction by TAT-fused peptide inhibits UFP-512 antidepressant-like and anxiolytic-like effects. | Kabli et al., 2013 |
| MOP-DOP receptor heteromer selective antibody | IHC, ELISA (chronic morphine treatment) | Increase of MOP-DOP receptor heteromers in various brain regions after chronic morphine treatment. | Gupta et al., 2010 |
i.m, intramuscularly; i.t, intrathecal; s.c., subcutaneously; i.c.v, intracerebroventricularly; IHC, immunohistochemistry.