NALMEFENE HYDROCHLORIDE DIHYDRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H25NO3.ClH.2H2O
Molecular Weight	411.92
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of NALMEFENE HYDROCHLORIDE DIHYDRATE

Structure Search

SMILES

O.O.Cl.[H][C@@]12OC3=C4C(C[C@H]5N(CC6CC6)CC[C@@]14[C@@]5(O)CCC2=C)=CC=C3O

InChI

InChIKey=XOBQQQVDLSMXCE-JVRGSUDVSA-N

InChI=1S/C21H25NO3.ClH.2H2O/c1-12-6-7-21(24)16-10-14-4-5-15(23)18-17(14)20(21,19(12)25-18)8-9-22(16)11-13-2-3-13;;;/h4-5,13,16,19,23-24H,1-3,6-11H2;1H;2*1H2/t16-,19+,20+,21-;;;/m1.../s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810044 | https://www.ncbi.nlm.nih.gov/pubmed/25187751 | https://www.ncbi.nlm.nih.gov/pubmed/25302021 | https://www.medicines.org.uk/emc/medicine/27609

Nalmefene is the first medication approved for alcoholism with the primary goal of reducing alcohol intake in an as needed approach. Nalmefene received a marketing authorization valid throughout the European Union on February 25, 2013 and is under development in Asia. Nalmefene is an opioid system modulator with a distinct μ, δ, and κ receptor profile. In vitro studies have demonstrated that Nalmefene is a selective opioid receptor ligand with antagonist activity at the μ and δ receptors and partial agonist activity at the κ receptor. In vivo studies have demonstrated that nalmefene reduces alcohol consumption, possibly by modulating cortico-mesolimbic functions. In the US, immediate-release injectable nalmefene was approved in 1995 as an antidote for opioid overdose. It was sold under the trade name Revex. The product was discontinued by its manufacturer around 2008. Currently Nalmefene is sold under the trade name Selincro. Selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking-risk level, without physical withdrawal symptoms and who do not require immediate detoxification.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Opioid receptors; mu/kappa/delta 33 Target ID: CHEMBL2095181 Sources: http://ec.europa.eu/health/documents/community-register/2013/20130225125325/anx_125325_en.pdf \| https://www.medicines.org.uk/emc/medicine/27609#PHARMACOLOGICAL_PROPS	Antagonist 2778
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19027293 \| http://ec.europa.eu/health/documents/community-register/2013/20130225125325/anx_125325_en.pdf	Antagonist 2778	0.44 nM [Ki]
Delta opioid receptor 77 Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19027293 \| http://ec.europa.eu/health/documents/community-register/2013/20130225125325/anx_125325_en.pdf	Antagonist 2778	9.3 nM [Ki]
Kappa opioid receptor 108 Target ID: CHEMBL237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19027293 \| http://ec.europa.eu/health/documents/community-register/2013/20130225125325/anx_125325_en.pdf	Partial Agonist 290	0.12 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alcoholism 19 Sources: http://ec.europa.eu/health/documents/community-register/2013/20130225125325/anx_125325_en.pdf	Primary		Approved 8429	Selincro Approved Use Selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking-risk level, without physical withdrawal symptoms and who do not require immediate detoxification. Launch Date 2013

C_max

Value	Dose	Analyte	Population
155 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
177 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
24.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
57.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
109 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3943269/	6 mg single, intravenous dose: 6 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1320 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
16.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877019/	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
16.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3943269/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1876 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
191 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3943269/	12 mg single, intravenous dose: 12 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
274 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
29.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877019/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
314 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
385 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3943269/	24 mg single, intravenous dose: 24 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
647 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
8.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3943269/	6 mg single, intravenous dose: 6 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877019/	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3943269/	12 mg single, intravenous dose: 12 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
10.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877019/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3943269/	24 mg single, intravenous dose: 24 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680580/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	NALMEFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
18 mg 1 times / day steady, oral Recommended Dose: 18 mg, 1 times / day Route: oral Route: steady Dose: 18 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30829564/	unhealthy, 39 years n = 1 Health Status: unhealthy Condition: alcohol dependence and Schizoaffective Disorder Age Group: 39 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/30829564/	Disc. AE: Psychiatric decompensation... AEs leading to discontinuation/dose reduction: Psychiatric decompensation (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30829564/
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3680580/	healthy, adult n = 4 Health Status: healthy Age Group: adult Sex: M Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/3680580/	Sources: https://pubmed.ncbi.nlm.nih.gov/3680580/
300 mg single, oral Highest studied dose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3680580/	healthy, adult n = 4 Health Status: healthy Age Group: adult Sex: M Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/3680580/	Sources: https://pubmed.ncbi.nlm.nih.gov/3680580/
0.75 ug/kg single, intravenous Highest studied dose Dose: 0.75 ug/kg Route: intravenous Route: single Dose: 0.75 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/	unhealthy, adult n = 3 Health Status: unhealthy Condition: postoperative pain Age Group: adult Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/	DLT: Anesthesia reversal... Dose limiting toxicities: Anesthesia reversal (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/
0.5 ug/kg single, intravenous MTD Dose: 0.5 ug/kg Route: intravenous Route: single Dose: 0.5 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/	unhealthy, adult n = 18 Health Status: unhealthy Condition: postoperative pain Age Group: adult Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/	DLT: Anesthesia reversal... Dose limiting toxicities: Anesthesia reversal (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/
20 mg 2 times / day steady, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/	unhealthy, adult n = 7 Health Status: unhealthy Condition: alcohol dependence Age Group: adult Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/	Disc. AE: Dizziness... AEs leading to discontinuation/dose reduction: Dizziness (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/
5 mg 2 times / day steady, oral Studied dose Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/	unhealthy, adult n = 7 Health Status: unhealthy Condition: alcohol dependence Age Group: adult Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/	Disc. AE: Dizziness, Rash... AEs leading to discontinuation/dose reduction: Dizziness (1 patient) Rash (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/

AEs

AE	Significance	Dose	Population
Psychiatric decompensation	1 patient Disc. AE	18 mg 1 times / day steady, oral Recommended Dose: 18 mg, 1 times / day Route: oral Route: steady Dose: 18 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30829564/	unhealthy, 39 years n = 1 Health Status: unhealthy Condition: alcohol dependence and Schizoaffective Disorder Age Group: 39 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/30829564/
Anesthesia reversal	2 patients DLT	0.75 ug/kg single, intravenous Highest studied dose Dose: 0.75 ug/kg Route: intravenous Route: single Dose: 0.75 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/	unhealthy, adult n = 3 Health Status: unhealthy Condition: postoperative pain Age Group: adult Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/
Anesthesia reversal	3 patients DLT	0.5 ug/kg single, intravenous MTD Dose: 0.5 ug/kg Route: intravenous Route: single Dose: 0.5 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/	unhealthy, adult n = 18 Health Status: unhealthy Condition: postoperative pain Age Group: adult Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/10754620/
Dizziness	1 patient Disc. AE	20 mg 2 times / day steady, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/	unhealthy, adult n = 7 Health Status: unhealthy Condition: alcohol dependence Age Group: adult Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/
Dizziness	1 patient Disc. AE	5 mg 2 times / day steady, oral Studied dose Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/	unhealthy, adult n = 7 Health Status: unhealthy Condition: alcohol dependence Age Group: adult Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/
Rash	1 patient Disc. AE	5 mg 2 times / day steady, oral Studied dose Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/	unhealthy, adult n = 7 Health Status: unhealthy Condition: alcohol dependence Age Group: adult Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7847600/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inducer 389 inhibitor 1767		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 MRP2 383 OATP1B1 788 OATP1B3 706 OCT1 512 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP3A4/5 278	UGT2B7 389 UGT1A3 422 UGT1A8 283 sulfotransferases 38 CYP3A4/5 85 P-gp 1537 BCRP 561 MRP2 205 OATP1B1 406 OATP1B3 350 OCT1 327	CYP1A2 701 CYP2A6 79 CYP2B6 547 CYP2C8 168 CYP2C19 293 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2A6 739	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2C8 965	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=23 Page: 23.0	no
MRP2 475	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
OCT1 543	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no

Drug as victim

Target	Modality	Activity
UGT1A3 422	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/product-information/selincro-epar-product-information_en.pdf#page=11 Page: 11.0	minor
UGT1A8 283	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/product-information/selincro-epar-product-information_en.pdf#page=11 Page: 11.0	minor
BCRP 561	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
MRP2 205	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
OATP1B1 406	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
OATP1B3 350	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
OCT1 327	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
P-gp 1537	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=14 Page: 14.0	no
CYP3A4/5 85	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/product-information/selincro-epar-product-information_en.pdf#page=11 Page: 11.0	yes
UGT2B7 389	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/product-information/selincro-epar-product-information_en.pdf#page=10 Page: 10.0	yes
sulfotransferases 38	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/product-information/selincro-epar-product-information_en.pdf#page=11 Page: 11.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.ema.europa.eu/en/documents/assessment-report/selincro-epar-public-assessment-report_en.pdf#page=12 Page: 12.0

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific, Inc. (AKSCI)	67672	http://www.aksci.com/item_detail.php?cat=67672
Achemtek	0104-005955	http://www.achemtek.com/55096-26-9
Alfa Chemistry	55096-26-9	https://www.alfa-chemistry.com/cas_55096-26-9.htm
Ambinter	Amb17618203	http://www.ambinter.com/reference/17618203
Ambinter	Amb22801010	http://www.ambinter.com/reference/22801010
ApexBio Technology	B5505	http://www.apexbt.com/nalmefene-d3.html
Aurora Fine Chemicals LLC	A17.877.204	http://online.aurorafinechemicals.com/info?ID=A17.877.204
BioChemPartner	BCP16723	http://www.biochempartner.com/55096-26-9-BCP16723
BioCrick	BCC6093	http://www.biocrick.com/Nalmefene-d3-BCC6093.html
ChemMol	49425127	http://www.chemmol.com/chemmol/49425127.html
ChemMol	99105242	http://www.chemmol.com/chemmol/99105242.html
Chemspace	CSSB00020660084	https://chem-space.com/CSSB00020660084
DC Chemicals	DC37635	http://www.dcchemicals.com//product_show-Nalmefene.html
Glentham Life Sciences	GP5746	http://www.glentham.com/products/product/GP5746/
Lab Network	LN01291034	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01291034
OChem	5964	http://www.ocheminc.com/index.php?act=psearch&pid=096N269
Sigma-Aldrich	N5770_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/n5770?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S536625	http://www.smolecule.com/products/s536625
THE BioTek	bt-276130	https://www.thebiotek.com/product/inhibitors/bt-276130

PubMed

Title	Date	PubMed
A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence.	1994 Oct	7847600
Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.	1998 Mar	9686407
Dynorphin A1-13 causes elevation of serum levels of prolactin through an opioid receptor mechanism in humans: gender differences and implications for modulation of dopaminergic tone in the treatment of addictions.	1999 Jan	9862779
Pharmacologic approaches to the management of alcoholism.	2001	11584870
New developments in the pharmacotherapy of alcohol dependence.	2001	11268820
Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence.	2001 Jun	11413242
Pharmacological control of opioid-induced pruritus: a quantitative systematic review of randomized trials.	2001 Jun	11412287
Mesa Grande: a methodological analysis of clinical trials of treatments for alcohol use disorders.	2002 Mar	11964100
Use of acamprosate and opioid antagonists in the treatment of alcohol dependence: a European perspective.	2003	14972781
Pharmacotherapy of alcohol dependence: a review of the clinical data.	2004	15182219
A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence.	2004 Aug	15232334
Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.	2004 Feb	14603266
Chronic administration of nalmefene leads to increased food intake and body weight gain in mice.	2004 Jul 8	15219821
Implantable technology for long-term delivery of nalmefene for treatment of alcoholism.	2004 Sep 28	15363499
Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling.	2006 Feb	16449486
Application of a sensitive liquid chromatographic/tandem mass spectrometric method to pharmacokinetic study of nalmefene in humans.	2007 Jun 1	17329173
Plasma met-enkephalin, beta-endorphin and leu-enkephalin levels in human hepatic encephalopathy.	2007 Mar-Apr	17684846
Effects of opioid receptor gene variation on targeted nalmefene treatment in heavy drinkers.	2008 Jul	18537939
[Pharmacokinetics of nalmefene after a single or multiple intravenous doses in Chinese healthy volunteers].	2008 Oct	18971181
The effects of herkinorin, the first mu-selective ligand from a salvinorin A-derived scaffold, in a neuroendocrine biomarker assay in nonhuman primates.	2008 Oct	18593955
Emerging drugs to treat alcoholism.	2010 Dec	20560783
Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.	2010 Jan 20	20091529
[Serum NT-proBNP levels in neonates with severe asphyxia and the effects of nalmefene on the NT-proBNP levels].	2010 Nov	21083993
Tailoring therapeutic strategies for treating posttraumatic stress disorder symptom clusters.	2010 Sep 7	20856915

Patents

Sample Use Guides

In Vivo Use Guide

How much to take - The recommended dose is one tablet on days when you think there is a risk you will drink alcohol - The maximum dose is one tablet per day. How and when to take - You should take the tablet 1-2 hours before you start drinking alcohol. - Swallow the tablet whole, do not crush or divide the tablet. - You can take Selincro (Nalmefene) with or without food. Each film-coated tablet contains 18.06 mg nalmefene (as hydrochloride dihydrate).

Route of Administration: Oral

In Vitro Use Guide

Nalmefene antagonized the bindings of [3H]-dihydromorphine, [3H]-ethylketocyclazocine and [3H]-D-ala-D-leu enkephalin with IC50's in the low nanomolar range in rat brain membranes.. At the central mu receptor, nalmefene bound with an IC50 of 1.0 nM

Name

Type

Language

NALMEFENE HYDROCHLORIDE DIHYDRATE

Common Name

English

SELINCRO

Brand Name

English

NALMEFENE HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

MORPHINAN-3,14-DIOL, 17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-6-METHYLENE-, HYDROCHLORIDE, HYDRATE (1:1:2), (5.ALPHA.)-

Common Name

English

Nalmefene hydrochloride dihydrate [WHO-DD]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

SELINCRO (AUTHORIZED: ALCOHOL-RELATED DISORDERS)