DEXTROMILNACIPRAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H22N2O
Molecular Weight	246.348
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin transporter 183 Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664	Inhibitor 8504	290.0 nM [Ki]
Serotonin transporter 183 Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664	Inhibitor 8504	16.9 nM [Ki]
Norepinephrine transporter 197 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664	Inhibitor 8504	139.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fibromyalgia 90 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022256s013lbl.pdf	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
Unknown 2596

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Analyte	Population
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

F_unbound

Value	Dose	Co-administered	Analyte	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946	inhibitor 2438 inducer 440	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other 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

Target	Modality	Activity
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022256lbl.pdf#page=18 Page: 18.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022256lbl.pdf#page=18 Page: 18.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022256lbl.pdf#page=18 Page: 18.0	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022256lbl.pdf#page=18 Page: 18.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022256lbl.pdf#page=18 Page: 18.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022256lbl.pdf#page=18 Page: 18.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022256lbl.pdf#page=18 Page: 18.0	no
CYP3A4/5 357	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0	no

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=7 Page: 7.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0	no	no (co-administration study) Comment: no changes in PK of warfarin or milnacipran were observed Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0	no	unlikely (co-administration study) Comment: when coadministered with carbamazepine, exposure (Cmax and AUC) to milnacipran decreased by 18% and 19%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0	no	unlikely (co-administration study) Comment: when coadministered with carbamazepine, exposure (Cmax and AUC) to milnacipran decreased by 18% and 19%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_PharmR_P2.pdf#page=59 Page: 59.0

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
Which bioequivalence study for a racemic drug? Application to milnacipran.	1998 Apr-Jun	9725476
[Side effects and its countermeasures of antidepressant].	2001 Aug	11519154
Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine.	2001 May	11354236
Does combined treatment with novel antidepressants and a dopamine D3 receptor agonist reproduce cocaine discrimination in rats?	2001 Nov-Dec	11985331
High-performance liquid chromatographic method to screen and quantitate seven selective serotonin reuptake inhibitors in human serum.	2001 Sep 25	11587344
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	12130856
Remarkable effect of milnacipran in the treatment of Japanese major depressive patients.	2002 Jun	12404688
Blood concentration of milnacipran in a case of a fatal automobile accident.	2002 Mar	11916015
Therapeutic effects of milnacipran, a serotonin and noradrenaline reuptake inhibitor, on post-stroke depression.	2002 May	11981353
In the rat forced swimming test, chronic but not subacute administration of dual 5-HT/NA antidepressant treatments may produce greater effects than selective drugs.	2002 Nov 15	12429415
The role of noradrenaline and selective noradrenaline reuptake inhibition in depression.	2002 Oct	12208564
A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression.	2002 Oct	12204314
Partial response and nonresponse to antidepressant therapy: current approaches and treatment options.	2002 Sep	12363125
Mechanism of action of antidepressants.	2002 Summer	12490828
[Psychotropic drugs used in a psychiatric hospital (pharmaco-epidemiologic aspects)].	2003	14681962
[Serotonin syndrome].	2003	12877005
[Pharmacokinetics and drug interaction of antidepressants and anti-manic drugs].	2003	12877004
[Adverse effects of antidepressants and antimanics].	2003	12877003
Therapeutic effects of milnacipran (serotonin noradrenalin reuptake inhibitor) on depression following mild and moderate traumatic brain injury.	2003 Aug	12928711
Differential period of onset of action of fluvoxamine, paroxetine and milnacipran for depression.	2003 Aug	12923828
Differential effects of milnacipran, fluvoxamine and paroxetine for depression, especially in gender.	2003 Dec	14680720
Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats.	2003 Dec	14573386
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	14640541
Milnacipran for the treatment of chronic pain.	2003 Oct	14533142
Effect of pindolol and milnacipran versus milnacipran and placebo on plasma prolactin and adrenocorticotrophic hormone in depressed subjects.	2003 Oct	14533141
Addition of a dopamine agonist, cabergoline, to a serotonin-noradrenalin reuptake inhibitor, milnacipran as a therapeutic option in the treatment of refractory depression: two case reports.	2003 Sep-Oct	14520161
Differential effects of fluvoxamine, paroxetine and milnacipran for depression, especially with regard to age.	2004 Aug	15303244
[Review of antidepressants from the TCAs to the third generation drugs].	2004 Dec	15825674
Acute effect of milnacipran on the relationship between the locus coeruleus noradrenergic and dorsal raphe serotonergic neuronal transmitters.	2004 Dec	15589386
A comparative study of milnacipran and paroxetine in outpatients with major depression.	2004 Dec	15555719
Characterization of the anxiolytic-like effects of fluvoxamine, milnacipran and risperidone in mice using the conditioned fear stress paradigm.	2004 Nov 3	15507225
Effectiveness of milnacipran for the treatment of chronic pain: a case series.	2004 Sep-Oct	15602099
Lithium augmentation in milnacipran-refractory depression for the prevention of relapse following electroconvulsive therapy.	2005 Jan-Feb	15660714
The effect of milnacipran (serotonin noradrenaline reuptake inhibitor) on memory in Korsakoff's syndrome after encephalitis.	2005 May-Jun	15882773

Patents

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 22:46:19 GMT 2025` Edited by `admin` on `Mon Mar 31 22:46:19 GMT 2025`
Record UNII	ES1O38J3C4
Record Status	`Validated (UNII)`
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Name

Type

Language

F-2696

Preferred Name

English

DEXTROMILNACIPRAN

Common Name

English

F2696

Code

English

(1R,2S)-MILNACIPRAN

Common Name

English

CYCLOPROPANECARBOXAMIDE, 2-(AMINOMETHYL)-N,N-DIETHYL-1-PHENYL-, (1R-CIS)-

Systematic Name

English

CYCLOPROPANECARBOXAMIDE, 2-(AMINOMETHYL)-N,N-DIETHYL-1-PHENYL-, (1R,2S)-

Systematic Name

English

Code System Code Type Description

FDA UNII

ES1O38J3C4