U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C32H34N4O6
Molecular Weight 570.6356
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NALDEMEDINE

SMILES

CC(C)(NC(=O)C1=C(O)[C@@H]2OC3=C(O)C=CC4=C3[C@@]25CCN(CC6CC6)[C@H](C4)[C@]5(O)C1)C7=NC(=NO7)C8=CC=CC=C8

InChI

InChIKey=AXQACEQYCPKDMV-RZAWKFBISA-N
InChI=1S/C32H34N4O6/c1-30(2,29-33-27(35-42-29)18-6-4-3-5-7-18)34-28(39)20-15-32(40)22-14-19-10-11-21(37)25-23(19)31(32,26(41-25)24(20)38)12-13-36(22)16-17-8-9-17/h3-7,10-11,17,22,26,37-38,40H,8-9,12-16H2,1-2H3,(H,34,39)/t22-,26+,31+,32-/m1/s1

HIDE SMILES / InChI
Molecular Formula C32H34N4O6
Molecular Weight 570.6356
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Naldemedine (Symproic) is an opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. Naldemedine is an opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid receptors. Naldemedine functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. Naldemedine is a derivative of naltrexone to which a side chain has been added that increases the molecular weight and the polar surface area, thereby reducing its ability to cross the blood-brain barrier (BBB). Naldemedine is also a substrate of the P-glycoprotein (P-gp) efflux transporter. Based on these properties, the CNS penetration of naldemedine is expected to be negligible at the recommended dose levels, limiting the potential for interference with centrally-mediated opioid analgesia. Naldemedine was approved in 2017 in both the US and Japan for the treatment of Opioid-induced Constipation.

CNS Activity

CNS Non-penetrant
1014
Curator's Comment: Naldemedine is a derivative of naltrexone to which a side chain has been added that increases the molecular weight and the polar surface area, thereby reducing its ability to cross the blood-brain barrier (BBB). Naldemedine is also a substrate of the P-glycoprotein (P-gp) efflux transporter. Based on these properties, the CNS penetration of naldemedine is expected to be negligible at the recommended dose levels, limiting the potential for interference with centrally-mediated opioid analgesia.

Originator

Approval Year

2017
422
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 161.08 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
Approved
8429
Symproic

Approved Use

SYMPROIC is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.

Launch Date

2017
Secondary
Approved
8429
SYMPROIC

Approved Use

SYMPROIC is an opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain

Launch Date

2017
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.98 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28960888
0.1 mg single, oral
dose: 0.1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALDEMEDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
11.6 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28960888
0.1 mg single, oral
dose: 0.1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALDEMEDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.3 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28960888
0.1 mg single, oral
dose: 0.1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALDEMEDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
100 mg single, oral
Highest studied dose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
healthy, 21.8 years
n = 6
Health Status: healthy
Age Group: 21.8 years
Sex: M
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
Other AEs: Abdominal pain, Diarrhea...
Other AEs:
Abdominal pain (16.7%)
Diarrhea (16.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
30 mg 1 times / day multiple, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
healthy, 28.3 years
n = 9
Health Status: healthy
Age Group: 28.3 years
Sex: M
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
Other AEs: Abdominal discomfort, Diarrhea...
Other AEs:
Abdominal discomfort (11.1%)
Diarrhea (11.1%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Disc. AE: Abdominal pain, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Abdominal pain (3.2%)
Diarrhea (3.2%)
Vomiting (3.2%)
Nausea (3.2%)
Colitis (0.1%)
Diverticulitis (0.1%)
Hematochezia (0.1%)
Transaminases abnormal (0.5%)
Edema peripheral (0.1%)
Hyperglycemia (0.1%)
Insomnia (0.1%)
Generalized spasm (0.1%)
Paralysis (0.1%)
Photosensitivity (0.1%)
Rash (0.1%)
Thrombosis (0.1%)
Supraventricular tachycardia (0.1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 16.7%
100 mg single, oral
Highest studied dose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
healthy, 21.8 years
n = 6
Health Status: healthy
Age Group: 21.8 years
Sex: M
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
Diarrhea 16.7%
100 mg single, oral
Highest studied dose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
healthy, 21.8 years
n = 6
Health Status: healthy
Age Group: 21.8 years
Sex: M
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
Abdominal discomfort 11.1%
30 mg 1 times / day multiple, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
healthy, 28.3 years
n = 9
Health Status: healthy
Age Group: 28.3 years
Sex: M
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
Diarrhea 11.1%
30 mg 1 times / day multiple, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
healthy, 28.3 years
n = 9
Health Status: healthy
Age Group: 28.3 years
Sex: M
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/28960888
Colitis 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Diverticulitis 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Edema peripheral 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Generalized spasm 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Hematochezia 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Hyperglycemia 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Insomnia 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Paralysis 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Photosensitivity 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Rash 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Supraventricular tachycardia 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Thrombosis 0.1%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Transaminases abnormal 0.5%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Abdominal pain 3.2%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Diarrhea 3.2%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Nausea 3.2%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Vomiting 3.2%
Disc. AE
0.2 mg 1 times / day steady, oral
Recommended
Dose: 0.2 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.2 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
unhealthy, adult
n = 1163
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 1163
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208854Orig1s000MedR.pdf
Page: p. 189
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
781

substrate
1737
inhibitor
1767

substrate
1037
inhibitor
1852

substrate
1217
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2C8
911

CYP2C19
1478

CYP2E1
882

CYP3A4/5
278

CYP4A11
21

OATP1B1
788

OATP1B3
706

OCT1
512

OCT2
647

OAT1
599

OAT3
642

BCRP
699

P-gp
1461
CYP1A2
1054

CYP2A6
543

CYP2B6
664

CYP2C8
693

CYP2E1
667

CYP2C19
991

UGT1A3
422

UGT1A1
418

UGT1A4
347

UGT1A6
307

UGT1A9
380

UGT2B4
249

UGT2B7
389

UGT2B15
203

UGT2B17
213

OATP1B1
406

OATP1B3
350

OCT1
327

OCT2
355

OAT1
326

OAT3
339

BCRP
561

P-gp
1537
UGT1A6
34

UGT2B7
14

UGT1A3
9

CYP1A2
701

CYP2B6
547
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2A6
739
 low or no [IC50 >20 uM]
CYP2B6
1001
 low or no [IC50 >20 uM]
CYP2D6
1891
 low or no [IC50 >20 uM]
CYP2E1
970
 low or no [IC50 >20 uM]
CYP4A11
25
 low or no [IC50 >20 uM]
CYP1A2
1692
 low or no [Inhibition 20 uM]
CYP2C19
1553
 low or no [Inhibition 20 uM]
CYP2C8
965
 low or no [Inhibition 20 uM]
CYP2C9
1819
 low or no [Inhibition 20 uM]
CYP3A4/5
335
 low or no
UGT1A3
93
 modest
BCRP
773
 no
CYP1A2
1692
 no
CYP3A4
1925
 no
OAT1
603
 no
OATP1B1
803
 no
OATP1B3
715
 no
OCT1
543
 no
P-gp
1650
 no
UGT1A6
141
 no
UGT2B7
157
 no
CYP2B6
1001
 not significant
OAT3
644
 weak
OCT2
648
 weak
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
561
 no
CYP1A2
1054
 no
CYP2A6
543
 no
CYP2B6
664
 no
CYP2C8
693
 no
CYP2C9
1037
 no
CYP2D6
1217
 no
CYP2E1
667
 no
OAT1
326
 no
OAT3
339
 no
OATP1B1
406
 no
OATP1B3
350
 no
OCT1
327
 no
OCT2
355
 no
UGT1A1
418
 no
UGT1A4
347
 no
UGT1A6
307
 no
UGT1A9
380
 no
UGT2B15
203
 no
UGT2B17
213
 no
UGT2B4
249
 no
UGT2B7
389
 no
CYP2C19
991
 yes
UGT1A3
422
 yes
CYP3A4
1737
 yes
yes (co-administration study)
Comment: administered with fluconazole and itraconazole (CYP3A4 inhibitors): itraconazole increased Cmax, AUC0-last, and AUC0-inf of naldemedine by 1.12-fold, 2.65-fold, and 2.91-fold, respectively; fluconazole increased Cmax, AUC0-last, and AUC0-inf of naldemedine by 1.38 fold, 1.88 fold, and 1.90 fold, respectively; adminstered with rifampin (CYP3A4 inducer):reduced naldemedine Cmax by ~39 % and AUCinf by ~83 %;
Page: 84.0
P-gp
1537
 yes
yes (co-administration study)
Comment: administered with cyclosporine (P-gp inhibitor): cyclosporine increased Cmax, AUClast and AUCinf of nalmedine by 1.45 fold, 1.79 fold and 1.78 fold, respectively;
Page: 15.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
AA Blocks
AA00JS9Z
https://www.aablocks.com/goods/Goods/detail?id=AA00JS9Z
Chem Scene
CS-0016072
http://www.chemscene.com/916072-89-4.html
Compound Cloud
54732242
Compound Cloud
56837137
MedChem Express
HY-19627
https://www.medchemexpress.com/naldemedine.html
MuseChem
I008228
https://www.musechem.com/product/I008228.html
ZINC
ZINC000100378061
http://zinc15.docking.org/substances/ZINC000100378061
eMolecules
194975367
eNovation Chemicals
D675473
https://enovationchem.com/ProductDetails.asp?ProductID=D675473
iChemical
EBD4054410
http://www.ichemical.com/products/916072-89-4.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
PubMed

PubMed

TitleDatePubMed
Naldemedine (Symproic) for opioid-induced constipation.
2017 Dec 4
Formulary Drug Review: Naldemedine.
2017 Jul
Spotlight on naldemedine in the treatment of opioid-induced constipation in adult patients with chronic noncancer pain: design, development, and place in therapy.
2018
Efficacy of Treatments for Opioid-Induced Constipation: Systematic Review and Meta-analysis.
2018 Oct
Patents

Patents

20090203723
2
20120135978
2
20130231485
2

Sample Use Guides

In Vivo Use Guide
Administration (2.1): • Alteration of analgesic dosing regimen prior to initiating SYMPROIC is not required • Patients receiving opioids for less than 4 weeks may be less responsive to SYMPROIC • Discontinue SYMPROIC if treatment with the opioid pain medication is also discontinued Dosage (2.2): • The recommended dosage of SYMPROIC is 0.2 mg orally once daily with or without food.
Route of Administration: Oral
In Vitro Use Guide
In binding assays, the IC50 and Ki values of S-297995 (Naldemedine) monotosylate for rat mu opioid receptor were 3.21 and 1.40 nM, respectively. S-297995 exhibited antagonistic activity with IC50 and Kb values for rat mu opioid receptor of 161.08 and 0.56 nM, respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:29:29 GMT 2023
Edited
by admin
on Sat Dec 16 01:29:29 GMT 2023
Record UNII
03KSI6WLXH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NALDEMEDINE
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
NALDEMEDINE [MI]
Common Name English
NALDEMEDINE [USAN]
Common Name English
17-(CYCLOPROPYLMETHYL)-6,7-DIDEHYDRO-4,5A-EPOXY-3,6,14-TRIHYDROXY-N-(2-(3-PHENYL-1,2,4-OXADIAZOL-5-YL)PROPAN-2-YL)MORPHINAN-7-CARBOXAMIDE
Common Name English
Naldemedine [WHO-DD]
Common Name English
naldemedine [INN]
Common Name English
S-297995
Code English
Classification Tree Code System Code
WHO-ATC A06AH05
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
NDF-RT N0000175691
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
Code System Code Type Description
INN
9484
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
DAILYMED
03KSI6WLXH
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
MERCK INDEX
m12021
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
CAS
916072-89-4
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
RXCUI
1876597
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
EVMPD
SUB177220
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
PUBCHEM
54732242
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
SMS_ID
100000163094
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
WIKIPEDIA
Naldemedine
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
USAN
ZZ-09
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
NCI_THESAURUS
C175156
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
DRUG CENTRAL
5220
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
ChEMBL
CHEMBL2105755
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
DRUG BANK
DB11691
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
FDA UNII
03KSI6WLXH
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
EPA CompTox
DTXSID501030350
Created by admin on Sat Dec 16 01:29:29 GMT 2023 , Edited by admin on Sat Dec 16 01:29:29 GMT 2023
PRIMARY
Related Record Type Details
Structure of NALDEMEDINE TOSYLATE
SALT/SOLVATE -> PARENT
KAPPA-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
Used recombinant human kappa-opioid receptor (expressed in HEK-293 cells), U-50488H as an agonist, and guanosine-5’-O-(3-(35S)thio) triphosphate ((35S)-GTP.GAMMA.S) as a ligand
ANTAGONIST
Kb
MU-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
Used recombinant human mu-opioid receptor (expressed in CHO-K1 cells), DAMGO as an agonist, and guanosine-5’-O-(3-(35S)thio) triphosphate ((35S)-GTP.GAMMA.S) as a ligand
ANTAGONIST
Kb
KAPPA-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
RECOMBINANT HUMAN KAPPA-OPIOID RECEPTOR (EXPRESSED IN HEK-293 CELLS), (3H)-U69593 AS A LIGAND
BINDING
Ki
MU-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
Kobs of (3H)-Naloxone was 0.233 (1/min).
BINDING
Association rate constant (Kobs)
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
DELTA-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
RECOMBINANT HUMAN DELTA-OPIOID RECEPTOR (EXPRESSED IN HEK-293 CELLS), (3H)-(D-ALA2, D-LEU5)-ENKEPHALIN (DADLE) AS A LIGAND
BINDING
Ki
MU-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
T1/2 of (3H)-Naloxone was 0.266 min.
BINDING
T1/2 (the time until binding of the radiolabelled ligand to the receptor decreases to 50% after addition of an excess amount of unlabeled ligand)
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
MU-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
Based on slope of Schild regression, naldemedine monotosylate exhibited non-competitive antagonism to morphine, oxycodone, hydrocodone, and fentanyl-induced (35S)-GTP.gamma.S binding.
NON-COMPETITIVE INHIBITOR
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MU-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
RECOMBINANT HUMAN MU-OPIOID RECEPTER (EXPRESSED IN CHO-K1 CELLS), (3H)-(D-ALA2, N-ME-PHE4, GLY5-OL)-ENKEPHALIN ACETATE SALT (DAMGO) AS A LIGAND
BINDING
Ki
DELTA-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
Used recombinant human delta-opioid receptor (expressed in HEK-293 cells), (Met5)-enkephalin as an agonist, and guanosine-5’-O-(3-(35S)thio) triphosphate ((35S)-GTP.GAMMA.S) as a ligand
ANTAGONIST
Kb
MU-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
Koff of (3H)-Naloxone was 0.266 (1/min).
BINDING
Dissociation rate constant (Koff)
Related Record Type Details
Structure of NOR-NALDEMEDINE
METABOLITE LESS ACTIVE -> PARENT
Structure of NALDEMEDINE-CARBOXYLIC ACID
METABOLITE LESS ACTIVE -> PARENT
Structure of BENZAMIDINE
METABOLITE INACTIVE -> PARENT
Structure of NALDEMEDINE 6-O-.BETA.-D-GLUCURONIDE
METABOLITE LESS ACTIVE -> PARENT
Structure of NALDEMEDINE-(7R)-7-HYDROXIDE
METABOLITE -> PARENT
Structure of NALDEMEDINE 3-O-.BETA.-D-GLUCURONIDE
METABOLITE INACTIVE -> PARENT
Related Record Type Details
Structure of NALDEMEDINE
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
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