Milnacipran (CHEM022343)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesXML
Record Information
Version1.0
Creation Date2016-05-25 18:28:55 UTC
Update Date2016-11-09 01:17:28 UTC
Accession NumberCHEM022343
Identification
Common NameMilnacipran
ClassSmall Molecule
DescriptionMilnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) and like many agents in this category was originally developed for and continues to be approved and indicated for the treatment of depression . Furthermore, in 2009 the US FDA approved milnacipran for the additional indication of treating fibromyalgia , although other regional regulatory authorities like the EMA, among others, have not yet approved the agent for such treatment, citing lack of robust evidence of efficacy, insufficient demonstration of maintenance of effect, and other concerns . Nevertheless, milnacipran demonstrates a somewhat unique characteristic among SNRIs to elicit a relatively balanced reuptake inhibition of both serotonin and noradrenaline, with a somewhat increased preference for noradrenaline reuptake inhibition - which is potentially a point of interest given the plausible proposal that noradrenaline plays an important role in the mitigation of pain signals in the descending inhibitory pain pathways in the brain and spinal cord . Moreover, recent research has shown that the levorotatory enantiomer of milnacipran, levomilnacipran, may have the capacity to inhibit the activity of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which has investigationally been associated with β-amyloid plaque formation - making the agent a possible course of treatment for Alzheimer's disease .
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
Contaminant TypeNot Available
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
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 Mass246.348 g/mol
Monoisotopic Mass246.173 g/mol
CAS Registry Number92623-85-3
IUPAC Name(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
Traditional Namemilnacipran
SMILESCCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C1=CC=CC=C1
InChI IdentifierInChI=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
Biological Properties
StatusDetected and Not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted 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
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-003s-9720000000-ca5db3dd96b3bf602e80Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001i-1590000000-14ea613049f0be797cc6Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0fai-2950000000-0d6b47bfb625a8443c78Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000t-0190000000-ac9945cd8c8043e9e92fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-008a-1980000000-989c19c8db76f07da08bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-5900000000-10e08ed18b692dc26d79Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-a43b5ce382df221bf86dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-4490000000-60028333af69e8af02bdSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00dl-9400000000-4f89e1fb8d13d48f3511Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0590000000-1f4d137f80628e35c827Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-2960000000-8f12df3429c555732cd0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00ba-6900000000-efba65f220764b405ef1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0290000000-722c0acf3966aec48c62Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-5290000000-6c41adc4efeb91c44163Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-4900000000-3e4a9ec417730d813614Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not Available
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB04896
HMDB IDHMDB0015602
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkMilnacipran
Chemspider ID59245
ChEBI ID521102
PubChem Compound ID65833
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
1. 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.
2. Briley M, Prost JF, Moret C: Preclinical pharmacology of milnacipran. Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14.
3. 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.
4. Puozzo C, Panconi E, Deprez D: Pharmacology and pharmacokinetics of milnacipran. Int Clin Psychopharmacol. 2002 Jun;17 Suppl 1:S25-35.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Simon LS: Is milnacipran effective in treating pain in patients with fibromyalgia? Nat Clin Pract Rheumatol. 2006 Mar;2(3):126-7.
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.
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.
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.