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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:52:03 UTC
HMDB IDHMDB0015602
Secondary Accession Numbers
  • HMDB15602
Metabolite Identification
Common NameMilnacipran
DescriptionMilnacipran, also known as F2207 or midalcipran, belongs to the class of organic compounds known as phenylacetamides. These are amide derivatives of phenylacetic acids. Milnacipran is a very strong basic compound (based on its pKa). During its development for fibromyalgia, milnacipran was evaluated utilizing a composite responder approach. As with other antidepressants, 1 to 3 weeks may elapse before significant antidepressant action becomes clinically evident. Administration of milnacipran should be done with caution in individuals with the following:Concomitant treatment with parenteral epinephrine, norepinephrine, with clonidine, reversible MAO-A Inhibitors (such as moclobemide, toloxatone) or 5-HT1D-agonists (e.g. triptan migraine drugs)Advanced renal disease (decreased dosage required)Hypertrophy of the prostate gland (possibly urination hesitancy induced), with hypertension and heart disease (tachycardia may be a problem) as well as with open angle glaucoma.Milnacipran should not be used during pregnancy because it may cross the placenta barrier and no clinical data exists on harmful effects in humans and animal studies. Recently, levomilnacipran, the levorotatory enantiomer of milnacipran, has been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for β-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease.
Structure
Data?1582753315
Synonyms
ValueSource
(-)-MilnacipranHMDB
F2207HMDB
MidalcipranHMDB
IxelHMDB
SavellaHMDB
LevomilnacipranHMDB
Milnacipran hydrochlorideHMDB
1-Phenyl-1-diethylaminocarbonyl-2-aminomethylcyclopropane HCLHMDB
FetzimaHMDB
1 Phenyl 1 diethylaminocarbonyl 2 aminomethylcyclopropane HCLHMDB
Chemical FormulaC15H22N2O
Average Molecular Weight246.348
Monoisotopic Molecular Weight246.173213336
IUPAC Name(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
Traditional Namemilnacipran
CAS Registry Number92623-85-3
SMILES
CCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C1=CC=CC=C1
InChI Identifier
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
InChI KeyGJJFMKBJSRMPLA-HIFRSBDPSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenylacetamides. These are amide derivatives of phenylacetic acids.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylacetamides
Direct ParentPhenylacetamides
Alternative Parents
Substituents
  • Phenylacetamide
  • Aralkylamine
  • Cyclopropanecarboxylic acid or derivatives
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Carboxamide group
  • Carboxylic acid derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organic nitrogen compound
  • Amine
  • Carbonyl group
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.23 g/LNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility1.23 g/LALOGPS
logP1.72ALOGPS
logP1.42ChemAxon
logS-2.3ALOGPS
pKa (Strongest Basic)9.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.33 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity73.81 m³·mol⁻¹ChemAxon
Polarizability28.03 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+158.73331661259
DarkChem[M-H]-155.22531661259
DeepCCS[M+H]+160.08930932474
DeepCCS[M-H]-157.73130932474
DeepCCS[M-2H]-190.61630932474
DeepCCS[M+Na]+166.18230932474
AllCCS[M+H]+157.532859911
AllCCS[M+H-H2O]+153.832859911
AllCCS[M+NH4]+160.932859911
AllCCS[M+Na]+161.832859911
AllCCS[M-H]-163.632859911
AllCCS[M+Na-2H]-163.932859911
AllCCS[M+HCOO]-164.332859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
MilnacipranCCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C1=CC=CC=C12979.1Standard polar33892256
MilnacipranCCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C1=CC=CC=C11991.8Standard non polar33892256
MilnacipranCCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C1=CC=CC=C11915.2Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Milnacipran,1TMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN[Si](C)(C)C2034.7Semi standard non polar33892256
Milnacipran,1TMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN[Si](C)(C)C2139.5Standard non polar33892256
Milnacipran,1TMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN[Si](C)(C)C2504.4Standard polar33892256
Milnacipran,2TMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN([Si](C)(C)C)[Si](C)(C)C2134.3Semi standard non polar33892256
Milnacipran,2TMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN([Si](C)(C)C)[Si](C)(C)C2369.7Standard non polar33892256
Milnacipran,2TMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN([Si](C)(C)C)[Si](C)(C)C2408.2Standard polar33892256
Milnacipran,1TBDMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN[Si](C)(C)C(C)(C)C2241.8Semi standard non polar33892256
Milnacipran,1TBDMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN[Si](C)(C)C(C)(C)C2385.5Standard non polar33892256
Milnacipran,1TBDMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN[Si](C)(C)C(C)(C)C2610.1Standard polar33892256
Milnacipran,2TBDMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C2554.1Semi standard non polar33892256
Milnacipran,2TBDMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C2765.7Standard non polar33892256
Milnacipran,2TBDMS,isomer #1CCN(CC)C(=O)[C@]1(C2=CC=CC=C2)C[C@@H]1CN([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C2606.2Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Milnacipran GC-MS (Non-derivatized) - 70eV, Positivesplash10-003s-9720000000-ca5db3dd96b3bf602e802017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Milnacipran GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Milnacipran , positive-QTOFsplash10-001i-1590000000-14ea613049f0be797cc62017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Milnacipran 35V, Positive-QTOFsplash10-0fai-2950000000-0d6b47bfb625a8443c782021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 10V, Positive-QTOFsplash10-000t-0190000000-ac9945cd8c8043e9e92f2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 20V, Positive-QTOFsplash10-008a-1980000000-989c19c8db76f07da08b2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 40V, Positive-QTOFsplash10-004i-5900000000-10e08ed18b692dc26d792016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 10V, Negative-QTOFsplash10-0002-0090000000-a43b5ce382df221bf86d2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 20V, Negative-QTOFsplash10-0002-4490000000-60028333af69e8af02bd2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 40V, Negative-QTOFsplash10-00dl-9400000000-4f89e1fb8d13d48f35112016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 10V, Positive-QTOFsplash10-0002-0590000000-1f4d137f80628e35c8272021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 20V, Positive-QTOFsplash10-0002-2960000000-8f12df3429c555732cd02021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 40V, Positive-QTOFsplash10-00ba-6900000000-efba65f220764b405ef12021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 10V, Negative-QTOFsplash10-0002-0290000000-722c0acf3966aec48c622021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 20V, Negative-QTOFsplash10-0002-5290000000-6c41adc4efeb91c441632021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Milnacipran 40V, Negative-QTOFsplash10-0006-4900000000-3e4a9ec417730d8136142021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB04896 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB04896 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB04896
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID59245
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMilnacipran
METLIN IDNot Available
PubChem Compound65833
PDB IDNot Available
ChEBI ID521102
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. [PubMed:16869117 ]
  2. Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. [PubMed:3005901 ]
  3. Briley M, Prost JF, Moret C: Preclinical pharmacology of milnacipran. Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14. [PubMed:8923122 ]
  4. Leinonen E, Lepola U, Koponen H, Mehtonen OP, Rimon R: Long-term efficacy and safety of milnacipran compared to clomipramine in patients with major depression. Acta Psychiatr Scand. 1997 Dec;96(6):497-504. [PubMed:9421348 ]
  5. Puozzo C, Panconi E, Deprez D: Pharmacology and pharmacokinetics of milnacipran. Int Clin Psychopharmacol. 2002 Jun;17 Suppl 1:S25-35. [PubMed:12369608 ]
  6. Moojen VK, Martins MR, Reinke A, Feier G, Agostinho FR, Cechin EM, Quevedo J: Effects of milnacipran in animal models of anxiety and memory. Neurochem Res. 2006 Apr;31(4):571-7. Epub 2006 May 9. [PubMed:16758367 ]
  7. Papakostas GI, Fava M: A meta-analysis of clinical trials comparing milnacipran, a serotonin--norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder. Eur Neuropsychopharmacol. 2007 Jan;17(1):32-6. Epub 2006 Jun 8. [PubMed:16762534 ]
  8. King T, Rao S, Vanderah T, Chen Q, Vardanyan A, Porreca F: Differential blockade of nerve injury-induced shift in weight bearing and thermal and tactile hypersensitivity by milnacipran. J Pain. 2006 Jul;7(7):513-20. [PubMed:16814690 ]
  9. Soya A, Terao T, Nakajima M, Kojima H, Okamoto T, Inoue Y, Iwakawa M, Shinkai K, Yoshimura R, Ueta Y, Nakamura J: Effects of repeated milnacipran administration on brain serotonergic and noradrenergic functions in healthy volunteers. Psychopharmacology (Berl). 2006 Sep;187(4):526-7. Epub 2006 Jul 8. [PubMed:16830129 ]
  10. Simon LS: Is milnacipran effective in treating pain in patients with fibromyalgia? Nat Clin Pract Rheumatol. 2006 Mar;2(3):126-7. [PubMed:16932669 ]
  11. Sato S, Yamakawa Y, Terashima Y, Ohta H, Asada T: Efficacy of milnacipran on cognitive dysfunction with post-stroke depression: preliminary open-label study. Psychiatry Clin Neurosci. 2006 Oct;60(5):584-9. [PubMed:16958942 ]
  12. Kako Y, Niwa Y, Toyomaki A, Yamanaka H, Kitagawa N, Denda K, Koyama T: A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):772-5. Epub 2007 Jan 12. [PubMed:17300859 ]
  13. Bernstein CD, Albrecht KL, Marcus DA: Milnacipran for fibromyalgia: a useful addition to the treatment armamentarium. Expert Opin Pharmacother. 2013 May;14(7):905-16. doi: 10.1517/14656566.2013.779670. Epub 2013 Mar 19. [PubMed:23506481 ]

Transporters

General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular weight:
69331.42
References
  1. Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. [PubMed:16869117 ]
  2. Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. [PubMed:3005901 ]
General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular weight:
70324.165
References
  1. Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. [PubMed:16869117 ]
  2. Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. [PubMed:3005901 ]