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Details

Stereochemistry RACEMIC
Molecular Formula C15H22N2O
Molecular Weight 246.348
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MILNACIPRAN

SMILES

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

InChI

InChIKey=GJJFMKBJSRMPLA-HIFRSBDPSA-N
InChI=1S/C15H22N2O/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12/h5-9,13H,3-4,10-11,16H2,1-2H3/t13-,15+/m1/s1

HIDE SMILES / InChI
Molecular Formula C15H22N2O
Molecular Weight 246.348
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: https://www.tga.gov.au/sites/default/files/auspar-milnacipran-hydrochloride-120124.pdf

Dextromilnacipran (1R, 2S/F2696) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Dextromilnacipran is pharmacologically less active as compared with racemic mixture and levomilnacipran (1S, 2R/F2695).

CNS Activity

Originator

Fabre, P.
12
Curator's Comment: Milnacipran was synthesised as a racemic mixture at the PIERRE FABRE MEDICAMENT Research Centre (Castres, France).

Approval Year

2009
364
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 290.0 nM [Ki]
Inhibitor
8504
 16.9 nM [Ki]
Inhibitor
8504
 139.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
SAVELLA

Approved Use

Savella is indicated for the management of fibromyalgia. Savella is not approved for use in pediatric patients [see Use in Specific Populations (8.4)

Launch Date

2009
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
132 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26663198/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
150 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8923123/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1316.9 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26663198/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26663198/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8923123/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022256s023lbl.pdf
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
87%
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8923123/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
87%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022256s023lbl.pdf
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MILNACIPRAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252

substrate
1946
inhibitor
2438

inducer
440
inhibitor
2507

substrate
1388
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
2153

CYP2A6
879

CYP2C19
2057

CYP2E1
1060
P-gp
2052

CYP2C19
1119

CYP1A2
1197
CYP1A2
832

CYP2B6
669

CYP2C8
198

CYP2C19
329

CYP3A4/5
133
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
2333
 no
CYP1A2
2333
 no
CYP2A6
911
 no
CYP2B6
1160
 no
CYP2C19
2141
 no
CYP2C19
2141
 no
CYP2C8
1117
 no
CYP2C9
2497
 no
CYP2C9
2497
 no
CYP2D6
2546
 no
CYP2E1
1146
 no
CYP3A4
2633
 no
CYP3A4/5
357
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
2052
 no
CYP2C19
1119
 no
no (co-administration study)
Comment: no changes in PK of warfarin or milnacipran were observed
Page: 55.0
CYP1A2
1197
 no
unlikely (co-administration study)
Comment: when coadministered with carbamazepine, exposure (Cmax and AUC) to milnacipran decreased by 18% and 19%, respectively;
Page: 55.0
CYP2D6
1388
 no
unlikely (co-administration study)
Comment: At steady state, Cmax and AUC for milnacipran increased by only 10% and 20% when coadministered with levomepromazine; no changes in PK of warfarin or milnacipran were observed
Page: 55.0
CYP3A4
1946
 no
unlikely (co-administration study)
Comment: when coadministered with carbamazepine, exposure (Cmax and AUC) to milnacipran decreased by 18% and 19%, respectively;
Page: 55.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
3B Scientific (Wuhan) Corp
3B2-6287
http://www.3bsc.com/index/pro_info.php?id=116365
Acorn PharmaTech
ACN-035533
http://www.acornpharmatech.com/
AK Scientific, Inc. (AKSCI)
R211
http://www.aksci.com/item_detail.php?cat=R211
Ambinter
Amb22801750
http://www.ambinter.com/reference/22801750
BioCrick
BCC4194
http://www.biocrick.com/Milnacipran-BCC4194.html
BLD Pharm
BD00756442
http://www.bldpharm.com/products/96847-55-1.html
BLD Pharm
BD631023
http://www.bldpharm.com/products/92623-85-3.html
Chem Scene
CS-2009
http://www.chemscene.com/92623-85-3.html
ChemMol
99177637
http://www.chemmol.com/chemmol/99177637.html
ChemMol
99185159
http://www.chemmol.com/chemmol/99185159.html
Clearsynth
CS-P-00447
http://www.clearsynth.com/en/CSP00447.html
CSNpharm
CSN18592
https://www.csnpharm.com/products/milnacipran.html
Hairui
HR143593
http://www.hairuichem.com/en/product/92623-85-3.html
iChemical
EBD2321826
http://www.ichemical.com/products/92623-85-3.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
Lab Network
LN01343162
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343162
MedChem Express
HY-B0168
https://www.medchemexpress.com/milnacipran.html
MuseChem
I012513
https://www.musechem.com/product/I012513.html
OChem
10310
http://www.ocheminc.com/index.php?act=psearch&pid=623M853
Sigma-Aldrich
CDS022174_ALDRICH
https://www.sigmaaldrich.com/catalog/product/aldrich/cds022174?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule
S006221
http://www.smolecule.com/products/s006221
Smolecule
S535456
http://www.smolecule.com/products/s535456
THE BioTek
bt-255210
https://www.thebiotek.com/product/inhibitors/bt-255210
THE BioTek
bt-276385
https://www.thebiotek.com/product/inhibitors/bt-276385
PubMed

PubMed

TitleDatePubMed
Which bioequivalence study for a racemic drug? Application to milnacipran.
1998 Apr-Jun
[Pharmacokinetics and drug interactions of antidepressive agents].
2001 Aug
[Serotonin-noradrenaline reuptake inhibitors(SNRIs)].
2001 Aug
Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine.
2001 May
Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype?
2002
Elevation of blood pressure induced by high-dose milnacipran.
2002 Dec
Conformational analysis of the NMDA receptor antagonist (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC) designed by a novel conformational restriction method based on the structural feature of cyclopropane ring.
2002 Jul
Neurochemical and behavioural characterization of milnacipran, a serotonin and noradrenaline reuptake inhibitor in rats.
2002 Jul
Blood concentration of milnacipran in a case of a fatal automobile accident.
2002 Mar
Silent thyroiditis associated with short-term lithium therapy.
2002 Nov-Dec
A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression.
2002 Oct
Effect of chronic treatment with milnacipran on sleep architecture in rats compared with paroxetine and imipramine.
2002 Oct
[Psychotropic drugs used in a psychiatric hospital (pharmaco-epidemiologic aspects)].
2003
[Experience with ixel (milnacipran hydrochloride) use in the treatment of patients with post-stroke depression].
2003
Differential period of onset of action of fluvoxamine, paroxetine and milnacipran for depression.
2003 Aug
Milnacipran and pindolol: a randomized trial of reduction of antidepressant latency.
2003 Dec
Differential effects of milnacipran, fluvoxamine and paroxetine for depression, especially in gender.
2003 Dec
A method for designing conformationally restricted analogues based on allylic strain: synthesis of a novel class of noncompetitive NMDA receptor antagonists having the acrylamide structure.
2003 Dec 4
Dual monoamine modulation for improved treatment of major depressive disorder.
2003 Feb
New hope in the treatment of painful symptoms in depression.
2003 Jan
Functional expression of the norepinephrine transporter in cultured rat astrocytes.
2003 Jan
Milnacipran for the treatment of chronic pain.
2003 Oct
Effect of pindolol and milnacipran versus milnacipran and placebo on plasma prolactin and adrenocorticotrophic hormone in depressed subjects.
2003 Oct
Favorable effect of milnacipran on depression induced by interferon-alpha.
2003 Spring
Efficacy of milnacipran for depressive symptoms in schizophrenia spectrum disorders.
2004 Apr
Milnacipran treatment of a terminally ill cancer patient with major depressive disorder.
2004 Aug
Ejaculation after defecation without orgasm induced by milnacipran.
2004 Fall
[Acute hepatitis associated with milnacipran treatment].
2004 Feb
Associations between baseline plasma MHPG (3-methoxy-4-hydroxyphenylglycol) levels and clinical responses with respect to milnacipran versus paroxetine treatment.
2004 Feb
Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity.
2004 Feb 1
Reboxetine: a norepinephrine selective reuptake pump inhibitor.
2004 Jan
Double-blind comparative study of the action of repeated administration of milnacipran versus placebo on cognitive functions in healthy volunteers.
2004 Jan
A case of temporo-mandibular disorder with fibromyalgia treated with the antidepressant, milnacipran.
2004 Jul
Augmentation of milnacipran by risperidone in treatment for major depression.
2004 Mar
Milnacipran, a serotonin and noradrenaline reuptake inhibitor, suppresses long-term potentiation in the rat hippocampal CA1 field via 5-HT1A receptors and alpha 1-adrenoceptors.
2004 Mar 4
The monoamine reuptake inhibitor milnacipran does not affect nociception to acute visceral distension in rats.
2004 May
Differential effects of milnacipran, fluvoxamine and paroxetine for inhibited and agitated depression.
2004 Nov
A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia.
2004 Oct
In vitro inhibition of recombinant ligand-gated ion channels by high concentrations of milnacipran.
2004 Sep
Effectiveness of milnacipran for the treatment of chronic pain: a case series.
2004 Sep-Oct
[Effects of milnacipran on neuronal excitability and synaptic transmission in neurons of the rat locus coeruleus].
2005 Jan
Lithium augmentation in milnacipran-refractory depression for the prevention of relapse following electroconvulsive therapy.
2005 Jan-Feb
Anxiolytic-like effect of milnacipran in the four-plate test in mice: mechanism of action.
2005 Jul
The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.
2005 May
Chronic treatment with milnacipran reverses the impairment of synaptic plasticity induced by conditioned fear stress.
2005 May
The effect of milnacipran (serotonin noradrenaline reuptake inhibitor) on memory in Korsakoff's syndrome after encephalitis.
2005 May-Jun
Patents

Patents

JP2003523410A
13
JP2007505097A
25
JP2007513956A
15
JP2010070573A
3
JP2010090143A
3
JP2011510954A
147
JP4549442B2
3
USRE43879
3

Sample Use Guides

In Vivo Use Guide
The recommended dose of Savella (Milnacipran) is 100 mg/day (50 mg twice daily). Based on efficacy and tolerability dosing may be titrated according to the following schedule: Day 1: 12.5 mg once Days 2-3: 25 mg/day (12.5 mg twice daily) Days 4-7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily) Based on individual patient response, the dose may be increased to 200 mg/day (100 mg twice daily). Doses above 200 mg/day have not been studied.
Route of Administration: Oral
In Vitro Use Guide
Milnacipran inhibits norepinephrine and serotonin reuptake in rat hypothalamic synaptosomes with IC50 values of 30 and 150 nM, respectively
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:32:43 GMT 2025
Edited
by admin
on Mon Mar 31 18:32:43 GMT 2025
Record UNII
G56VK1HF36
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IMPULSOR
Preferred Name English
MILNACIPRAN
EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
Milnacipran [WHO-DD]
Common Name English
MILNACIPRAN [MI]
Common Name English
milnacipran [INN]
Common Name English
(1RS,2SR)-2-(AMINOMETHYL)-N,N-DIETHYL-1-PHENYLCYCLOPROPANECARBOXAMIDE
Systematic Name English
MILNACIPRAN [VANDF]
Common Name English
MILNACIPRAN [EMA EPAR]
Common Name English
MILNACIPRAN PIERRE FABRE MEDICAMENT
Brand Name English
CYCLOPROPANECARBOXAMIDE, 2-(AMINOMETHYL)-N,N-DIETHYL-1-PHENYL-, (1R,2S)-REL-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C29747
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
WHO-VATC QN06AX17
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
EMA ASSESSMENT REPORTS IMPULSOR (REFUSED, FIBROMYALGIA)
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
NDF-RT N0000000109
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
NCI_THESAURUS C265
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
NDF-RT N0000175749
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
NDF-RT N0000000102
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
LIVERTOX NBK547960
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
EMA ASSESSMENT REPORTS MILNACIPRAN PIERRE FABRE MEDICAMENT (REFUSED: FIBROMYALGIA)
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
WHO-ATC N06AX17
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
EMA ASSESSMENT REPORTS IMPULSOR (REFUSED: FIBROMYALGIA)
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
Code System Code Type Description
MESH
C048107
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
RXCUI
588250
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY RxNorm
WIKIPEDIA
MILNACIPRAN
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
NCI_THESAURUS
C78021
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
IUPHAR
7436
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
ChEMBL
CHEMBL259209
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
FDA UNII
G56VK1HF36
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
SMS_ID
100000080634
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
EPA CompTox
DTXSID3048287
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
MERCK INDEX
m7545
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY Merck Index
LACTMED
Milnacipran
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
DRUG BANK
DB04896
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
INN
5701
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
DAILYMED
G56VK1HF36
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
DRUG CENTRAL
1808
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
CAS
92623-85-3
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
EVMPD
SUB08965MIG
Created by admin on Mon Mar 31 18:32:43 GMT 2025 , Edited by admin on Mon Mar 31 18:32:43 GMT 2025
PRIMARY
Related Record Type Details
Structure of MILNACIPRAN HYDROCHLORIDE
SALT/SOLVATE -> PARENT
Structure of MILNACIPRAN
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
The plasma protein binding of milnacipran is approximately 13% and is independent of the concentration (Study# M013).
BINDING
Structure of DEXTROMILNACIPRAN
ENANTIOMER -> RACEMATE
Structure of LEVOMILNACIPRAN
ENANTIOMER -> RACEMATE
Related Record Type Details
Structure of MILNACIPRAN CARBAMOYL O-GLUCURONIDE, L-
METABOLITE -> PARENT
MAJOR
URINE
Structure of MILNACIPRAN CARBAMOYL O-GLUCURONIDE, D-
METABOLITE -> PARENT
MINOR
URINE
Structure of N-DESETHYL MILNACIPRAN
METABOLITE -> PARENT
Lower than detection limit in plasma
MAJOR
URINE
Related Record Type Details
Structure of CYCLOPROPANECARBOXYLIC ACID, 2-(AMINOMETHYL)-1-PHENYL-, CIS-
IMPURITY -> PARENT
Related Record Type Details
Structure of MILNACIPRAN
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Structure of MILNACIPRAN
Absolute Bioavailability PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Structure of MILNACIPRAN
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

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