Levomilnacipran

drug

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Also known as (1s,2r)-milnacipranF 2695F-2695F2695Milnacipran, (1s,2r)-d-Milnacipran

Summary

Levomilnacipran (CHEMBL99946) is an approved small molecule (ATC N06AX28) targeting SLC6A2, SLC6A3, and SLC6A4; indicated across 2 conditions including depressive disorder and nicotine dependence.

At a glance

Status: Approved (max clinical phase 4)
Modality: Small molecule
ATC class: N06AX28
Targets: 3 (SLC6A2, SLC6A3, SLC6A4)
Indications: 2 conditions
Clinical trials: 9
Chemistry: 246.35 Da · C15H22N2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL99946
Name	Levomilnacipran
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	6917779
ATC	N06AX28
Molecular formula	C15H22N2O
Molecular weight	246.35
InChIKey	GJJFMKBJSRMPLA-DZGCQCFKSA-N

SMILES: CCN(CC)C(=O)[C@]1(C[C@H]1CN)C2=CC=CC=C2

IUPAC name: cis-(1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide

Also known as: (1s,2r)-milnacipran, F 2695, F-2695, F2695, Levomilnacipran, Milnacipran, (1s,2r)-, LEVOMILNACIPRAN, d-Milnacipran

Parent form; salt/anhydrous children: CHEMBL2105732

Patent coverage: 547 distinct patent families (1,352 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

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
SLC6A2	NET	Inhibition	7.4	0.4%	P23975
SLC6A3	DAT	Inhibition	5.49	0.2%	Q01959
SLC6A4	SERT	Inhibition	6.49	0.7%	P31645

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Glutamate NMDA receptor, Sodium-dependent noradrenaline transporter, Sodium-dependent serotonin transporter, Sodium-dependent dopamine transporter, Sodium-dependent serotonin transporter.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 15 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P31652	8.07	Ki	8.5	nM	CHEMBL_ACT_367357
P31652	8.07	Ki	8.5	nM	CHEMBL_ACT_409913
SLC6A2	7.98	IC50	10.5	nM	CHEMBL_ACT_25521256
SLC6A2	7.4	IC50	40	nM	CHEMBL_ACT_2169347
SLC6A2	7.4	IC50	40	nM	CHEMBL_ACT_2170769
SLC6A4	6.5	IC50	320	nM	CHEMBL_ACT_2169393
SLC6A4	6.5	IC50	320	nM	CHEMBL_ACT_2170770
SLC6A3	5.5	IC50	3200	nM	CHEMBL_ACT_2169440
SLC6A3	5.5	IC50	3200	nM	CHEMBL_ACT_2170771
SLC6A3	5.5	IC50	3200	nM	CHEMBL_ACT_25521261
P35439	5.2	IC50	6300	nM	CHEMBL_ACT_1308228
P35439	5.2	IC50	6300	nM	CHEMBL_ACT_178315
P35439	5.2	IC50	6300	nM	CHEMBL_ACT_367355
P35439	5.2	IC50	6300	nM	CHEMBL_ACT_409912

Target pathways

Aggregated over 3 target gene(s): SLC6A2, SLC6A3, SLC6A4.

Top Reactome pathways

15 total, by targets touching each:

Pathway	Targets	Genes
SLC-mediated transport of neurotransmitters	3	SLC6A2, SLC6A3, SLC6A4
Neurotransmitter clearance	2	SLC6A3, SLC6A4
Transmission across Chemical Synapses	2	SLC6A3, SLC6A4
Neuronal System	2	SLC6A3, SLC6A4
Disease	2	SLC6A2, SLC6A3
Transport of small molecules	2	SLC6A2, SLC6A3
R-HSA-425366	2	SLC6A2, SLC6A3
SLC-mediated transmembrane transport	2	SLC6A2, SLC6A3
SLC transporter disorders	2	SLC6A2, SLC6A3
Disorders of transmembrane transporters	2	SLC6A2, SLC6A3
Dopamine clearance from the synaptic cleft	1	SLC6A3
Serotonin clearance from the synaptic cleft	1	SLC6A4
Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	SLC6A3
Defective SLC6A2 causes orthostatic intolerance (OI)	1	SLC6A2
Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	SLC6A3

Dominant GO biological processes

GO term	Targets
neurotransmitter transport	3
amino acid transport	3
response to xenobiotic stimulus	3
obsolete monoamine transport	3
sodium ion transmembrane transport	3
transmembrane transport	3
dopamine uptake involved in synaptic transmission	2
norepinephrine uptake	2
neurotransmitter reuptake	2
chemical synaptic transmission	1
obsolete norepinephrine transport	1
response to pain	1
neuron cellular homeostasis	1
catecholamine uptake	1
chloride transmembrane transport	1

Indications & clinical

Indications

2 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
depressive disorder	4	MONDO:0002050	MONDO:0002009
nicotine dependence	0	MONDO:0008575	EFO:0003768

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE3	4
PHASE4	3
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02466958	PHASE4	COMPLETED	Trial of Levomilnacipran in Geriatric Depression
NCT03128021	PHASE4	COMPLETED	Neural Mechanisms of Monoaminergic Engagement in Late-life Depression Treatment Response (NEMO)
NCT03249311	PHASE4	UNKNOWN	Levomilnacipran in Healthy Males
NCT01639014	PHASE3	COMPLETED	Effect of F2695 on Functional Recovery After Ischemic Stroke
NCT02431806	PHASE3	COMPLETED	Safety and Efficacy of Levomilnacipran ER in Adolescent Participants With Major Depressive Disorder
NCT02720198	PHASE3	COMPLETED	Levomilnacipran ER vs. Adjunctive Quetiapine for Adults With Inadequate Relief With SSRIs in MDD
NCT07253207	PHASE3	COMPLETED	Efficacy and Safety Study of Levomilnacipran Hydrochloride Extended-Release Capsules in Major Depressive Disorder
NCT02266966	PHASE1	COMPLETED	Effect of F2695 on Brain Activity Measured by Functional Magnetic Resonance Imaging
NCT02265367	Not specified	COMPLETED	Novel Medication as a Potential Smoking Cessation Aid

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for desvenlafaxine, duloxetine, fluoxetin	CPIC	HTR2A
Annotation of CPIC Guideline for citalopram, desvenlafaxine, duloxetin	CPIC	SLC6A4

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.

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

Molecule	Source	Status	Shared targets
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
Idelalisib	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
Olodaterol	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
Tadalafil	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
TAFENOQUINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
UMECLIDINIUM	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
AMIODARONE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
AMOXAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
ASENAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
ATOMOXETINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BENFLUOREX	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BENZTROPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BENZYDAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BEPRIDIL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BOSUTINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BROMHEXINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BROMPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
BUPROPION	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CABERGOLINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CALCITRIOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CARBINOXAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CARVEDILOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CELECOXIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CETIRIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CHLORPHENTERMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CINACALCET	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CINNARIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CITALOPRAM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CLEMASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CLOMIPHENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
COBIMETINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
COCAINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
DANAZOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
DEQUALINIUM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
DESIPRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
DESLORATADINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4
DESOGESTREL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3, SLC6A4

Genes: SLC6A2, SLC6A3, SLC6A4
Diseases: depressive disorder
Drugs: Afatinib, Amitriptyline, Crizotinib, Idelalisib, Olodaterol, Pimavanserin, Regorafenib, Tadalafil, Tafenoquine, Umeclidinium, Vorapaxar, Acetophenazine, Amiodarone, Amoxapine, Aripiprazole, Asenapine, Astemizole, Atomoxetine, Azelastine, Bazedoxifene, Benfluorex, Benzphetamine, Benztropine, Benzydamine, Bepridil, Bosutinib, Brexpiprazole, Bromhexine, Bromodiphenhydramine, Bromperidol, Brompheniramine, Bupropion, Cabergoline, Calcitriol, Carbinoxamine, Carvedilol, Celecoxib, Cetirizine, Chlorhexidine, Chlorpheniramine, Chlorphentermine, Chlorpromazine, Chlorprothixene, Cinacalcet, Cinnarizine, Citalopram, Clemastine, Clomiphene, Clomipramine, Clotrimazole, Cobimetinib, Cocaine, Cyproheptadine, Danazol, Daunorubicin, Dequalinium, Desipramine, Desloratadine, Desogestrel

Summary

Identifiers

Drug identity and classification

Targets

Targets

Bioactivity

Target pathways

Top Reactome pathways

Dominant GO biological processes

Indications & clinical

Indications

Clinical trials

Phase distribution

Top trials by phase / activity

Clinical evidence (CIViC)

Pharmacology

Pharmacogenomics

Related molecules

Related molecules

Related Atlas pages