Identification
NameNomifensine
Accession NumberDB04821
TypeSmall Molecule
GroupsWithdrawn
Description

Nomifensine, formerly marketed as Merital capsules, was associated with an increased incidence of hemolytic anemia. The approved application holder removed Merital capsules from the market on January 23, 1986. FDA published a notice of its determination that Merital capsules were removed from the market for safety reasons (see the Federal Register of June 17, 1986 (51 FR 21981)). Approval of the NDA for Merital capsules was withdrawn on March 20, 1992 (see the Federal Register of March 20, 1992 (57 FR 9729)). Also withdrawn from the Canadian and UK markets.

Structure
Thumb
Synonyms
(+-)-nomifensin
(+-)-nomifensine
(+)-nomifensine
(+)-nomiphensine
(R)-1,2,3,4-Tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine
2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine
8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisochinolin
8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline
8-Amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline
Nomifensin
Nomifensina
Nomifensinum
External IDs Not Available
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LinamiphenNot Available
MeritalNot Available
NomifenisonNot Available
Brand mixturesNot Available
Categories
UNII1LGS5JRP31
CAS number24526-64-5
WeightAverage: 238.3275
Monoisotopic: 238.146998586
Chemical FormulaC16H18N2
InChI KeyXXPANQJNYNUNES-UHFFFAOYSA-N
InChI
InChI=1S/C16H18N2/c1-18-10-14(12-6-3-2-4-7-12)13-8-5-9-16(17)15(13)11-18/h2-9,14H,10-11,17H2,1H3
IUPAC Name
2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-amine
SMILES
CN1CC(C2=CC=CC=C2)C2=C(C1)C(N)=CC=C2
Pharmacology
IndicationNot Available
Structured Indications Not Available
Pharmacodynamics

Nomifensine is a dopamine reuptake inhibitor test-marketed in the United States by Hoechst AG (now Novartis) that increases the amount of synaptic dopamine available to receptors by blocking dopamine's re-uptake transporter. Nomifensine is now mainly used in scientific research, particularly in studies involving dopamine release in response to addiction.

Mechanism of action
TargetKindPharmacological actionActionsOrganismUniProt ID
Sodium-dependent noradrenaline transporterProteinunknownNot AvailableHumanP23975 details
Sodium-dependent dopamine transporterProteinunknownNot AvailableHumanQ01959 details
Amine oxidase [flavin-containing] BProteinunknownNot AvailableHumanP27338 details
Amine oxidase [flavin-containing] AProteinunknownNot AvailableHumanP21397 details
MyeloperoxidaseProteinunknownNot AvailableHumanP05164 details
Sodium-dependent serotonin transporterProteinunknownNot AvailableHumanP31645 details
Synaptic vesicular amine transporterProteinunknownNot AvailableHumanQ05940 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
Toxicity

A likely cause of nomifensine toxicity is the aromatic amine group, as compounds containing this chemical substructure are notorious for producing toxic metabolites.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceUS3577424
General ReferencesNot Available
External Links
ATC CodesN06AX04 — Nomifensine
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials Not Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)180 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.318 mg/mLALOGPS
logP2.94ALOGPS
logP2.62ChemAxon
logS-2.9ALOGPS
pKa (Strongest Basic)8.88ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.26 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity77.18 m3·mol-1ChemAxon
Polarizability27.56 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9837
Caco-2 permeable+0.7206
P-glycoprotein substrateSubstrate0.5814
P-glycoprotein inhibitor INon-inhibitor0.8827
P-glycoprotein inhibitor IINon-inhibitor0.6448
Renal organic cation transporterNon-inhibitor0.5406
CYP450 2C9 substrateNon-substrate0.8614
CYP450 2D6 substrateNon-substrate0.545
CYP450 3A4 substrateNon-substrate0.5637
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9404
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6612
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9183
BiodegradationNot ready biodegradable0.9692
Rat acute toxicity2.9821 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9534
hERG inhibition (predictor II)Inhibitor0.7539
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as 4-phenyltetrahydroisoquinolines. These are compounds containing a phenyl group attached to the C4-atom of a tetrahydroisoquinoline moiety.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassTetrahydroisoquinolines
Direct Parent4-phenyltetrahydroisoquinolines
Alternative ParentsAminoquinolines and derivatives / Aralkylamines / Primary aromatic amines / Benzene and substituted derivatives / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents4-phenyltetrahydroisoquinoline / Aminoquinoline / Aralkylamine / Monocyclic benzene moiety / Primary aromatic amine / Benzenoid / Tertiary amine / Tertiary aliphatic amine / Azacycle / Primary amine
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsisoquinolines (CHEBI:116225 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Norepinephrine: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
Uniprot Name:
Sodium-dependent noradrenaline transporter
Molecular Weight:
69331.42 Da
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Uniprot Name:
Sodium-dependent dopamine transporter
Molecular Weight:
68494.255 Da
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Primary amine oxidase activity
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
Uniprot Name:
Amine oxidase [flavin-containing] B
Molecular Weight:
58762.475 Da
References
  1. Egashira T, Takayama F, Yamanaka Y: The inhibition of monoamine oxidase activity by various antidepressants: differences found in various mammalian species. Jpn J Pharmacol. 1999 Sep;81(1):115-21. [PubMed:10580379 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serotonin binding
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Uniprot Name:
Amine oxidase [flavin-containing] A
Molecular Weight:
59681.27 Da
References
  1. Egashira T, Takayama F, Yamanaka Y: The inhibition of monoamine oxidase activity by various antidepressants: differences found in various mammalian species. Jpn J Pharmacol. 1999 Sep;81(1):115-21. [PubMed:10580379 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Peroxidase activity
Specific Function:
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
Gene Name:
MPO
Uniprot ID:
P05164
Uniprot Name:
Myeloperoxidase
Molecular Weight:
83867.71 Da
References
  1. Obach RS, Dalvie DK: Metabolism of nomifensine to a dihydroisoquinolinium ion metabolite by human myeloperoxidase, hemoglobin, monoamine oxidase A, and cytochrome P450 enzymes. Drug Metab Dispos. 2006 Aug;34(8):1310-6. Epub 2006 May 5. [PubMed:16679384 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serotonin: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 an...
Gene Name:
SLC6A4
Uniprot ID:
P31645
Uniprot Name:
Sodium-dependent serotonin transporter
Molecular Weight:
70324.165 Da
References
  1. Henry LK, Field JR, Adkins EM, Parnas ML, Vaughan RA, Zou MF, Newman AH, Blakely RD: Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants. J Biol Chem. 2006 Jan 27;281(4):2012-23. Epub 2005 Nov 3. [PubMed:16272152 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis.
Gene Name:
SLC18A2
Uniprot ID:
Q05940
Uniprot Name:
Synaptic vesicular amine transporter
Molecular Weight:
55712.075 Da
References
  1. Gonzalez AM, Walther D, Pazos A, Uhl GR: Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. [PubMed:7912402 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
no
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Uniprot Name:
Alpha-1-acid glycoprotein 1
Molecular Weight:
23511.38 Da
References
  1. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. [PubMed:2870173 ]
Drug created on September 11, 2007 14:22 / Updated on July 07, 2017 03:05