OLICERIDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H30N2O2S
Molecular Weight	386.551
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

COC1=C(CNCC[C@]2(CCOC3(CCCC3)C2)C4=NC=CC=C4)SC=C1

InChI

InChIKey=DMNOVGJWPASQDL-OAQYLSRUSA-N

InChI=1S/C22H30N2O2S/c1-25-18-7-15-27-19(18)16-23-13-10-21(20-6-2-5-12-24-20)11-14-26-22(17-21)8-3-4-9-22/h2,5-7,12,15,23H,3-4,8-11,13-14,16-17H2,1H3/t21-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C22H30N2O2S
Molecular Weight	386.551
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Oliceridine (TRV-130) is a potent μ-opioid receptor agonist. In cell-based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less β-arrestin recruitment and receptor internalization. In rodents, TRV130 is potently analgesic while causing less gastrointestinal dysfunction and respiratory suppression than morphine at equianalgesic doses. Oliceridine is being developed by Trevena for the first-line treatment of moderate-to-severe acute postoperative pain. Phase III development is underway for the treatment of postoperative pain in the US. Phase II development is underway for the treatment of acute pain in the US.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 221	Agonist 2,678		8.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614	Primary		Phase III 656	Unknown

C_max

Value	Dose	Analyte	Population
2.29 μg/L	0.25 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
3.09 μg/L	0.25 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
45.2 μg/L	1.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
54.7 μg/L	1.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
81.3 μg/L	3 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
54 μg/L	3 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
127.8 μg/L	4.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
117.3 μg/L	4.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
239.7 μg/L	6 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
183.8 μg/L	6 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
19.5 pg/mL	100 μg single, oral	OLICERIDINE plasma	Homo sapiens
34.8 ng/mL	1 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
41.4 ng/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
41.9 ng/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
8.4 ng/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
4.94 ng/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
8.79 ng/mL	1 mg single, intravenous	OLICERIDINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
374.18 ng × h/mL	27 mg 12 times / day multiple, intravenous	OLICERIDINE plasma	Homo sapiens
5.29 μg × h/L	0.25 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
11.14 μg × h/L	0.25 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
39.1 μg × h/L	1.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
75.6 μg × h/L	1.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
73.8 μg × h/L	3 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
136.6 μg × h/L	3 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
229.3 μg × h/L	4.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
108.2 μg × h/L	4.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
171.59 μg × h/L	6 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
243 μg × h/L	6 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
134 pg × h/mL	100 μg single, oral	OLICERIDINE plasma	Homo sapiens
23.7 ng × h/mL	1 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
22.5 ng × h/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
29.5 ng × h/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
23.9 ng × h/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
10.2 ng × h/mL	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
18.1 ng × h/mL	1 mg single, intravenous	OLICERIDINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
1.567 h	27 mg 12 times / day multiple, intravenous	OLICERIDINE plasma	Homo sapiens
1.56 h	0.25 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
2.82 h	0.25 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
1.7 h	1.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
3.49 h	1.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
1.67 h	3 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
3.6 h	3 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
3.64 h	4.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
1.7 h	4.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
3.63 h	6 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
4.07 h	6 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
1.62 h	100 μg single, oral	OLICERIDINE plasma	Homo sapiens
2.07 h	1 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
2.61 h	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
4.33 h	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
5.77 h	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
2.99 h	0.5 mg single, intravenous	OLICERIDINE plasma	Homo sapiens
2.34 h	1 mg single, intravenous	OLICERIDINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
23%			OLICERIDINE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
27 mg multiple, intravenous Recommended	unhealthy, ADULT	Disc. AE: Opioid abuse, Opioid type dependence...
7 mg single, intravenous Studied dose	healthy, ADULT

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AEs

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AE	Significance	Dose	Population
Opioid abuse	Disc. AE	27 mg multiple, intravenous Recommended	unhealthy, ADULT
Opioid type dependence	Disc. AE	27 mg multiple, intravenous Recommended	unhealthy, ADULT
QT interval prolonged	Disc. AE	27 mg multiple, intravenous Recommended	unhealthy, ADULT
Neonatal opioid withdrawal syndrome	grade 4 Disc. AE	27 mg multiple, intravenous Recommended	unhealthy, ADULT
Respiratory depression	grade 5 Disc. AE	27 mg multiple, intravenous Recommended	unhealthy, ADULT

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PubMed

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Title	Date	PubMed
Biased agonism of the μ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers.	2014 Sep	24954166

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Patents

Sample Use Guides

In Vivo Use Guide

Oliceridine dosed at 2mg or 3mg every 3 hours demonstrated a tolerability profile similar to morphine dosed at 4mg every 4 hours, in a randomised, double-blind, placebo-controlled, 48-hour phase IIa/b trial in patients with acute postoperative pain after bunionectomy

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical
Record UNII	MCN858TCP0
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

OLICERIDINE

Official Name

English

Oliceridine [WHO-DD]

Common Name

English

TRV130

Code

English

oliceridine [INN]

Common Name

English

TRV-130

Code

English

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Classification Tree

Code System

Code

Sec. 1308.11 Schedule V.

DEA NO.

9245

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Code System

Code

Type

Description

CAS

1401028-24-7

PRIMARY

DRUG BANK

DB14881

PRIMARY

INN

10250

PRIMARY

NCI_THESAURUS

C174704

PRIMARY

MERCK INDEX

m12219

PRIMARY

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Interaction Type:

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Amount:

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(3S,5R,7R)-7-(2-((3-METHOXY-2-THIENYL)METHYLAMINO)ETHYL)-7-(2-PYRIDYL)-10-OXASPIRO(4.5)DECAN-3-OL

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OLICERIDINE

ACTIVE MOIETY

Showing 1 to 1 of 1 entries

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Name	Property Type	Amount	Parameters
Volume of Distribution	PHARMACOKINETIC	[90 to 120] LITERS (average)	AT STEADY-STATE

Tmax	PHARMACOKINETIC	0.12 hours [0.11 to 0.28] (average)	SINGLE DOSE INTRAVENOUS ADMINISTRATION

Biological Half-life	PHARMACOKINETIC	1.8 hours [1.3 to 3] (average)	INTRAVENOUS ADMINISTRATION SINGLE DOSE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound