Nalmefene

Summary

Nalmefene (CHEMBL982) is an approved small molecule (ATC N07BB05) targeting OPRD1, OPRK1, and OPRM1; indicated across 8 conditions including alcohol abuse and drug dependence.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N07BB05
• Targets: 3 (OPRD1, OPRK1, OPRM1)
• Indications: 8 conditions
• Clinical trials: 33
• Chemistry: 339.4 Da · C21H25NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL982
Name	Nalmefene
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5284594
ATC	N07BB05
Molecular formula	C21H25NO3
Molecular weight	339.4
InChIKey	WJBLNOPPDWQMCH-MBPVOVBZSA-N

SMILES: C=C1CC[C@]2([C@H]3CC4=C5[C@]2([C@H]1OC5=C(C=C4)O)CCN3CC6CC6)O

IUPAC name: (4R,4aS,7aS,12bS)-3-(cyclopropylmethyl)-7-methylidene-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol

Also known as: JF-1, JKB-121, Nalmefene, Nalmefeno, Nalmetrene, ORF 1167, ORF 11676, ORF-1167, ORF-11676, Selincro, SRD-174, SRD174

Parent form; salt/anhydrous children: CHEMBL1201152, CHEMBL5315055

Patent coverage: 3,164 distinct patent families (12,908 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 12,423 (96%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
OPRD1	δ receptor	Partial agonist	8.1	0.2%	P41143
OPRK1	κ receptor	Antagonist	9.5	0%	P41145
OPRM1	μ receptor	Antagonist	9.5	0%	P35372

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Delta-type opioid receptor, Mu-type opioid receptor, Nuclear receptor subfamily 1 group I member 2, Kappa-type opioid receptor.

Bioactivity

ChEMBL activities: 26 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRK1	10.08	Ki	0.08	nM	CHEMBL_ACT_16742568
OPRK1	9.92	Ki	0.12	nM	CHEMBL_ACT_2263857
OPRM1	9.62	Ki	0.24	nM	CHEMBL_ACT_16742569
P33535	9.54	Ki	0.29	nM	CHEMBL_ACT_418938
OPRM1	9.53	Kd	0.3	nM	CHEMBL_ACT_2115992
OPRM1	9.52	Ki	0.3	nM	CHEMBL_ACT_25943331
OPRM1	9.36	Ki	0.44	nM	CHEMBL_ACT_2263855
OPRM1	9.04	Ki	0.91	nM	CHEMBL_ACT_2115840
OPRD1	9.04	Kd	0.91	nM	CHEMBL_ACT_2116003
OPRM1	9.04	Ki	0.91	nM	CHEMBL_ACT_3070009
OPRK1	8.99	Ki	1.03	nM	CHEMBL_ACT_2115894
OPRK1	8.99	Ki	1.03	nM	CHEMBL_ACT_3070030
OPRM1	8.7	IC50	2	nM	CHEMBL_ACT_29322743
P41144	8.7	Ki	2	nM	CHEMBL_ACT_418939
P33533	8.47	Ki	3.4	nM	CHEMBL_ACT_418940
OPRK1	8.1	IC50	7.94	nM	CHEMBL_ACT_29322791
OPRD1	8.03	Ki	9.3	nM	CHEMBL_ACT_2263856
OPRD1	7.88	Ki	13.26	nM	CHEMBL_ACT_2115867
OPRD1	7.88	Ki	13.26	nM	CHEMBL_ACT_3070020
OPRD1	7.8	Ki	16	nM	CHEMBL_ACT_16742567
OPRK1	7.75	AC50	18	nM	CHEMBL_ACT_25129611
OPRD1	7.09	AC50	82	nM	CHEMBL_ACT_25154266
OPRD1	6.9	IC50	125.9	nM	CHEMBL_ACT_29322839
OPRK1	6.11	IC50	779	nM	CHEMBL_ACT_5564986
OPRM1	5.68	IC50	2100	nM	CHEMBL_ACT_29322759
OPRK1	5.12	IC50	7600	nM	CHEMBL_ACT_29322807

Target pathways

Aggregated over 3 target gene(s): OPRD1, OPRK1, OPRM1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	3	OPRD1, OPRK1, OPRM1
G alpha (i) signalling events	3	OPRD1, OPRK1, OPRM1
Interleukin-4 and Interleukin-13 signaling	2	OPRD1, OPRM1
MECP2 regulates neuronal receptors and channels	2	OPRK1, OPRM1
Opioid Signalling	1	OPRM1
G-protein activation	1	OPRM1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	3
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	3
phospholipase C-activating G protein-coupled receptor signaling pathway	3
neuropeptide signaling pathway	3
G protein-coupled opioid receptor signaling pathway	3
signal transduction	3
immune response	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
response to nicotine	2
eating behavior	2
response to ethanol	2
sensory perception	2
sensory perception of pain	2
adult locomotory behavior	1
negative regulation of gene expression	1

Indications & clinical

Indications

8 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
alcohol abuse	4	MONDO:0002046	MONDO:0007079
drug dependence	3	MONDO:0005303	EFO:0003890
pathological gambling	2	MONDO:0011662	EFO:0004699
atopic eczema	2	MONDO:0004980	EFO:0000274
metabolic dysfunction-associated steatohepatitis	2	MONDO:0007027	EFO:1001249
opiate dependence	1	MONDO:0005530	EFO:0005611
kidney disorder	1	MONDO:0005240	EFO:0003086

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 33.

Phase distribution

Phase	Trials
PHASE1	13
PHASE3	7
PHASE2	5
PHASE4	3
Not specified	3
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02197598	PHASE4	COMPLETED	Treatment of Patients Suffering of Alcohol Dependence and Impaired Liver Function With Selincro® As-needed Use
NCT04713358	PHASE4	COMPLETED	Effect of Nalmefene on the Quality of Resuscitation in Patients Under General Anesthesia
NCT05808881	PHASE4	WITHDRAWN	Clinical Outcomes From Nalmefene
NCT05540288	PHASE3	RECRUITING	NAlmefene Versus Placebo in Addition to Treatment as Usual on Craving in Behavioural Addictions
NCT00811720	PHASE3	COMPLETED	Efficacy of Nalmefene in Patients With Alcohol Dependence
NCT00811941	PHASE3	COMPLETED	Safety and Efficacy of Nalmefene in Patients With Alcohol Dependence
NCT00812461	PHASE3	COMPLETED	Efficacy of Nalmefene in Patients With Alcohol Dependence
NCT02364947	PHASE3	COMPLETED	A Multicenter, Randomized, Double-blind, Placebo-controlled, 3-parallel-group Comparison Trial to Investigate the Effect of Nalmefene on Alcohol Consumption Reduction in Patients With Alcohol Dependence (Phase 3 Trial)
NCT02382276	PHASE3	COMPLETED	A Long-term Extension Study for the Phase 3 Study of Nalmefene (339-14-001) in Patients With Alcohol Dependence
NCT06408714	PHASE3	WITHDRAWN	Nalmefene vs Naloxone for the Treatment of Recurrent Respiratory Depression After Opioid Overdose
NCT06733519	PHASE2	NOT_YET_RECRUITING	TH104 for the Treatment of Pruritus in Primary Biliary Cholangitis
NCT00202696	PHASE2	COMPLETED	Nalmefene Smoking Cessation Study
NCT00838708	PHASE2	COMPLETED	Phase IIa Safety and Efficacy Study of SRD174 Cream in Patients With AD-associated Pruritus
NCT02934919	PHASE2	UNKNOWN	Evaluation of Nalmefene in Impulse Control Disorders in Parkinson’s Disease: A Prospective Open Label Study
NCT03034408	PHASE2	COMPLETED	Nalmefene, Baclofen and Impulsivity in Subjects With Alcohol Use Disorder and Healthy Control Subjects
NCT03278886	PHASE1/PHASE2	COMPLETED	St. PETERsburg Pain and Alcohol Intervention With Naltrexone and Nalmefene
NCT05338632	PHASE1	RECRUITING	Reversal of Opioid-induced Respiratory Depression With Opioid Antagonists
NCT01934166	PHASE1	COMPLETED	Pharmacokinetic Properties of Nalmefene in Subjects With Renal Impairment and in Healthy Subjects
NCT01969617	PHASE1	COMPLETED	Effects of Nalmefene After Single Dose on the Blood Oxygen Level Dependent (BOLD) fMRI Signal in the Ventral Striatum to Reward Responding in the Monetary Incentive Delay Task (MIDT), in Non-treatment Seeking Subjects With Alcohol Dependence Following Alcohol Challenge
NCT02639273	PHASE1	COMPLETED	Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation
NCT02679469	PHASE1	COMPLETED	A Single-center, Open-label, Single-dose Study Investigating the Safety, Tolerability, and Pharmacokinetic Properties of Nalmefene 10 mg Tablets in Healthy Japanese Male Subjects
NCT03129347	PHASE1	COMPLETED	Pharmacokinetic Evaluation of Nalmefene Administered Intranasally to Healthy Volunteers
NCT03279562	PHASE1	COMPLETED	Patient Driven Recovery With Nalmefene and Coaching
NCT04759768	PHASE1	COMPLETED	Pharmacokinetic Evaluation of Intranasal Nalmefene
NCT04828005	PHASE1	COMPLETED	Pharmacodynamic Evaluation of Intranasal Nalmefene
NCT05219669	PHASE1	COMPLETED	Pharmacokinetic Evaluation of Intranasal Nalmefene Using Three Dosing Regimens
NCT06198686	PHASE1	COMPLETED	An Evaluation of The Absolute Bioavailability of TH104
NCT06719986	PHASE1	COMPLETED	Pharmacodynamic Evaluation of Intramuscular Nalmefene Autoinjector 1.5 mg Compared to Intranasal Narcan 4 mg
NCT07543276	PHASE1	COMPLETED	Pharmacokinetic (PK) Evaluation of Nalmefene Formulations
NCT02372318	EARLY_PHASE1	TERMINATED	Single-dose of Nalmefene to Modulate Neural Alcohol Cue Reactivity
NCT02492581	Not specified	COMPLETED	Use of Selincro and Impact on Usual Practice
NCT02752503	Not specified	UNKNOWN	Nalmefene in Alcohol Dependence and Borderline Personality Disorder
NCT03096730	Not specified	COMPLETED	Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 5 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

612 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CODEINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ECONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FENTANYL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LANSOPRAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LEVORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOPERAMIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MEPERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHADONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHYLNALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MICONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALBUPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALFURAFINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALOXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NELFINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OLICERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PAROXETINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PASIREOTIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PENTAZOCINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PIMOZIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RALOXIFENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RITONAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAMIDORPHAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAQUINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SUNITINIB	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAMOXIFEN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TRAMADOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASIMADOLINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
ATICAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
CEBRANOPADOL	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
NAVACAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
TRIMEBUTINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
BREMAZOCINE	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1
CARFENTANIL	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1