Identification

Name
Nomifensine
Accession Number
DB04821
Type
Small Molecule
Groups
Withdrawn
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 Approval of the NDA for Merital capsules was withdrawn on March 20, 1992 (see the Federal Register of March 20, 1992 (57 FR 9729)). Also withdrawn from the Canadian and UK markets.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
International/Other Brands
Linamiphen / Merital / Nomifenison
Categories
UNII
1LGS5JRP31
CAS number
24526-64-5
Weight
Average: 238.3275
Monoisotopic: 238.146998586
Chemical Formula
C16H18N2
InChI Key
XXPANQJNYNUNES-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

Indication
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
TargetActionsOrganism
USodium-dependent noradrenaline transporterNot AvailableHuman
USodium-dependent dopamine transporterNot AvailableHuman
UAmine oxidase [flavin-containing] BNot AvailableHuman
UAmine oxidase [flavin-containing] ANot AvailableHuman
UMyeloperoxidaseNot AvailableHuman
USodium-dependent serotonin transporterNot AvailableHuman
USynaptic vesicular amine transporterNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmikacinThe risk or severity of adverse effects can be increased when Nomifensine is combined with Amikacin.Approved, Investigational, Vet Approved
BenzphetamineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Benzphetamine.Approved, Illicit
Benzyl alcoholThe risk or severity of adverse effects can be increased when Benzyl alcohol is combined with Nomifensine.Approved
Botulinum Toxin Type BThe risk or severity of adverse effects can be increased when Nomifensine is combined with Botulinum Toxin Type B.Approved, Investigational
BrompheniramineThe risk or severity of adverse effects can be increased when Brompheniramine is combined with Nomifensine.Approved
BupropionThe risk or severity of adverse effects can be increased when Bupropion is combined with Nomifensine.Approved
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Nomifensine.Approved, Investigational
CetirizineThe risk or severity of adverse effects can be increased when Cetirizine is combined with Nomifensine.Approved
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Nomifensine.Approved
ClemastineThe risk or severity of adverse effects can be increased when Clemastine is combined with Nomifensine.Approved, Investigational
ClindamycinThe risk or severity of adverse effects can be increased when Nomifensine is combined with Clindamycin.Approved, Vet Approved
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Nomifensine.Approved, Illicit
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Nomifensine.Approved
CyclosporineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Cyclosporine.Approved, Investigational, Vet Approved
DesvenlafaxineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Desvenlafaxine.Approved, Investigational
DexbrompheniramineThe risk or severity of adverse effects can be increased when Dexbrompheniramine is combined with Nomifensine.Approved
DimenhydrinateThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Nomifensine.Approved
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Nomifensine.Approved, Investigational
DotarizineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Dotarizine.Investigational
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Nomifensine.Approved, Vet Approved
EperisoneThe risk or severity of adverse effects can be increased when Nomifensine is combined with Eperisone.Approved, Investigational
EthanolNomifensine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.Approved
EthosuximideThe risk or severity of adverse effects can be increased when Ethosuximide is combined with Nomifensine.Approved
EtomidateThe risk or severity of adverse effects can be increased when Etomidate is combined with Nomifensine.Approved
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Nomifensine.Approved, Illicit, Investigational, Vet Approved
FlunarizineThe risk or severity of adverse effects can be increased when Flunarizine is combined with Nomifensine.Approved
FluoxetineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Fluoxetine.Approved, Vet Approved
FluspirileneThe risk or severity of adverse effects can be increased when Fluspirilene is combined with Nomifensine.Approved, Investigational
Fluticasone propionateThe risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Nomifensine.Approved
FluvoxamineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Fluvoxamine.Approved, Investigational
GabapentinThe risk or severity of adverse effects can be increased when Gabapentin is combined with Nomifensine.Approved, Investigational
GuanfacineThe risk or severity of adverse effects can be increased when Guanfacine is combined with Nomifensine.Approved, Investigational
HydrocodoneNomifensine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.Approved, Illicit
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Nomifensine.Approved
LamotrigineThe risk or severity of adverse effects can be increased when Lamotrigine is combined with Nomifensine.Approved, Investigational
LevetiracetamThe risk or severity of adverse effects can be increased when Levetiracetam is combined with Nomifensine.Approved, Investigational
LevodopaThe risk or severity of adverse effects can be increased when Levodopa is combined with Nomifensine.Approved
LoratadineThe risk or severity of adverse effects can be increased when Loratadine is combined with Nomifensine.Approved, Investigational
Magnesium carbonateThe risk or severity of adverse effects can be increased when Nomifensine is combined with Magnesium carbonate.Approved, Investigational
Magnesium citrateThe risk or severity of adverse effects can be increased when Nomifensine is combined with Magnesium citrate.Approved
Magnesium hydroxideThe risk or severity of adverse effects can be increased when Nomifensine is combined with Magnesium hydroxide.Approved, Investigational
Magnesium sulfateThe therapeutic efficacy of Nomifensine can be increased when used in combination with Magnesium sulfate.Approved, Investigational, Vet Approved
Magnesium TrisilicateThe risk or severity of adverse effects can be increased when Nomifensine is combined with Magnesium Trisilicate.Approved
MeclizineThe risk or severity of adverse effects can be increased when Meclizine is combined with Nomifensine.Approved
MethsuximideThe risk or severity of adverse effects can be increased when Methsuximide is combined with Nomifensine.Approved
NeomycinThe risk or severity of adverse effects can be increased when Nomifensine is combined with Neomycin.Approved, Vet Approved
OndansetronThe risk or severity of adverse effects can be increased when Ondansetron is combined with Nomifensine.Approved
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Nomifensine.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Nomifensine.Approved, Investigational, Vet Approved
ParomomycinThe risk or severity of adverse effects can be increased when Nomifensine is combined with Paromomycin.Approved, Investigational
ParoxetineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Paroxetine.Approved, Investigational
PenfluridolThe risk or severity of adverse effects can be increased when Penfluridol is combined with Nomifensine.Experimental
PhenobarbitalThe risk or severity of adverse effects can be increased when Phenobarbital is combined with Nomifensine.Approved, Investigational
Polymyxin B SulfateThe risk or severity of adverse effects can be increased when Nomifensine is combined with Polymyxin B Sulfate.Approved, Vet Approved
PramipexoleNomifensine may increase the sedative activities of Pramipexole.Approved, Investigational
PregabalinThe therapeutic efficacy of Nomifensine can be increased when used in combination with Pregabalin.Approved, Illicit, Investigational
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Nomifensine.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Nomifensine.Approved, Investigational
PseudoephedrineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Pseudoephedrine.Approved
PyrantelThe risk or severity of adverse effects can be increased when Nomifensine is combined with Pyrantel.Approved, Vet Approved
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Nomifensine.Approved
RizatriptanThe risk or severity of adverse effects can be increased when Nomifensine is combined with Rizatriptan.Approved
RopiniroleNomifensine may increase the sedative activities of Ropinirole.Approved, Investigational
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Nomifensine.Approved, Investigational
SumatriptanThe risk or severity of adverse effects can be increased when Nomifensine is combined with Sumatriptan.Approved, Investigational
TetracyclineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Tetracycline.Approved, Vet Approved
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Tetrahydropalmatine is combined with Nomifensine.Investigational
TopiramateThe risk or severity of adverse effects can be increased when Topiramate is combined with Nomifensine.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Nomifensine.Approved, Investigational
TrimethadioneThe risk or severity of adverse effects can be increased when Nomifensine is combined with Trimethadione.Approved
Valproic AcidThe risk or severity of adverse effects can be increased when Valproic Acid is combined with Nomifensine.Approved, Investigational
VancomycinThe risk or severity of adverse effects can be increased when Nomifensine is combined with Vancomycin.Approved
VecuroniumThe risk or severity of adverse effects can be increased when Nomifensine is combined with Vecuronium.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Nomifensine.Approved
VenlafaxineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Venlafaxine.Approved
VinpocetineThe risk or severity of adverse effects can be increased when Nomifensine is combined with Vinpocetine.Investigational
ZiconotideThe risk or severity of adverse effects can be increased when Ziconotide is combined with Nomifensine.Approved
ZolmitriptanThe risk or severity of adverse effects can be increased when Nomifensine is combined with Zolmitriptan.Approved, Investigational
ZolpidemNomifensine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.Approved
ZonisamideThe risk or severity of adverse effects can be increased when Zonisamide is combined with Nomifensine.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference
US3577424
General References
Not Available
External Links
PubChem Compound
4528
PubChem Substance
46505804
ChemSpider
4371
BindingDB
50005548
ChEBI
116225
ChEMBL
CHEMBL273575
Therapeutic Targets Database
DCL000339
Wikipedia
Nomifensine
ATC Codes
N06AX04 — Nomifensine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 4-phenyltetrahydroisoquinolines. These are compounds containing a phenyl group attached to the C4-atom of a tetrahydroisoquinoline moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Tetrahydroisoquinolines
Sub Class
4-phenyltetrahydroisoquinolines
Direct Parent
4-phenyltetrahydroisoquinolines
Alternative Parents
Aminoquinolines and derivatives / Aralkylamines / Benzene and substituted derivatives / Trialkylamines / Azacyclic compounds / Primary amines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
4-phenyltetrahydroisoquinoline / Aminoquinoline / Aralkylamine / Benzenoid / Monocyclic benzene moiety / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
isoquinolines (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...
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...
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 o...
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 t...
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...
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...
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 August 02, 2018 05:26