Table 1 G protein–biased ligands at the μ-OR.

ND, no data available.

LigandIn vitroIn vivoReference
G protein activationβ-Arrestin recruitmentAdministration and
dose
Outcome
Oliceridine (TRV130)EC50 = 7.94 nM
Efficacy = 84%
EC50 = 5.01 nM
Efficacy = 15%
ND(81)
EC50 = 8 nM
Efficacy = 71%
Efficacy = 14%C57BL/6J mice•Peak analgesia in 5 min(82)
Subcutaneous, 1 mg/kg•Reduced central
nervous system
depression and
gastrointestinal
dysfunction
NDNDPhase I trial•Well tolerated(102)
18 healthy volunteers•Nausea and vomiting
at 7 mg limited further
dose escalation
Intravenous, dose
range 0.15 to 7 mg
NDNDPhase II trial•2 and 3 mg mitigated
severe acute pain over
48 hours
(103)
Pilot phase:
144 patients
After pilot phase:
195 patients
Intravenous, 0.5, 1, 2, or
3 mg every 3 hours
NDNDPhase III trial•Superior analgesia(104)
375 patients•Reduced respiratory
side effects and
increased
gastrointestinal
tolerability
Intravenous: 1.5 mg
loading dose followed
by 0.1-mg, 0.35-mg, or
0.5-mg doses
Morphine (4-mg
loading dose; 1-mg
demand dose)
Mitragynine
pseudoindoxyl
EC50 = 1.7 nM
Efficacy = 84%
No recruitment at
10 μM
CD-1 mice•Analgesia(105)
Subcutaneous,
0.76 mg/kg
•Limited respiratory
depression and
constipation
SHR9352EC50 = 0.77 nM
Efficacy = 96%
EC50 = 2.5 nM
Efficacy = 18%
C57BL/6J mice and
Wistar rats
•Analgesia(106)
Subcutaneous, 0.1 mg
or
•No constipation
Intravenous, 0.3 mg
SR-17018EC50 = 97 nM
Efficacy = 75%
No recruitment at
10 μM
C57BL/6J mice•Analgesia(107)
Intraperitoneal,
6 mg/kg
•No respiratory
suppression
HerkinorinEC50 = 0.5 μMNo recruitment at
10 μM
No blood-brain barrier
penetration
(108)
PZM21EC50 = 4.6 nM
Efficacy = 76%
No recruitment at
10 μM
C57BL/6J mice•Dose dependent
response
(97)
Subcutaneous, 40, 20,
and 10 mg/kg
•Long-lasting analgesia
•Decreased respiratory
depression and
constipation
CyclopeptideEC50 = 5.2 nM
Efficacy = 80%
No recruitment at
10 μM
ND(109)