U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C16H18N2
Molecular Weight 238.3275
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NOMIFENSINE

SMILES

CN1CC(C2=CC=CC=C2)C3=C(C1)C(N)=CC=C3

InChI

InChIKey=XXPANQJNYNUNES-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C16H18N2
Molecular Weight 238.3275
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Nomifensine was developed by Hoechst AG as a potent inhibitor of noradrenaline, dopamine, and 5-HT uptake displayed antidepressant activity. It was first marketed in the UK in 1977 for the treatment of depression. Between 1977 and 1982 there were reports of hemolytic anemia in association with the drug, and this suspected adverse reaction was included in the 1981 edition of the data Sheet Compendium. FDA published a notice of its determination that Merital capsules were removed from the market for safety reasons.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.7 nM [Ki]
26.0 nM [Ki]
4.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
84 μg/L
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NOMIFENSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
53 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NOMIFENSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
196.8 μg × h/L
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NOMIFENSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.9 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NOMIFENSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.2 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NOMIFENSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
25%
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NOMIFENSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
150 mg 2 times / day multiple, oral
Studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, 18-44 years
n = 18
Health Status: unhealthy
Condition: attention deficit disorder
Age Group: 18-44 years
Sex: M+F
Population Size: 18
Sources:
Disc. AE: Skin rash, Fever...
AEs leading to
discontinuation/dose reduction:
Skin rash (severe, 1 patient)
Fever (severe, 1 patient)
Back pain (severe, 1 patient)
Sources:
100 mg single, intravenous
Dose: 100 mg
Route: intravenous
Route: single
Dose: 100 mg
Sources:
healthy, 22-41 years
Health Status: healthy
Age Group: 22-41 years
Sex: M+F
Sources:
AEs

AEs

AESignificanceDosePopulation
Back pain severe, 1 patient
Disc. AE
150 mg 2 times / day multiple, oral
Studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, 18-44 years
n = 18
Health Status: unhealthy
Condition: attention deficit disorder
Age Group: 18-44 years
Sex: M+F
Population Size: 18
Sources:
Fever severe, 1 patient
Disc. AE
150 mg 2 times / day multiple, oral
Studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, 18-44 years
n = 18
Health Status: unhealthy
Condition: attention deficit disorder
Age Group: 18-44 years
Sex: M+F
Population Size: 18
Sources:
Skin rash severe, 1 patient
Disc. AE
150 mg 2 times / day multiple, oral
Studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources:
unhealthy, 18-44 years
n = 18
Health Status: unhealthy
Condition: attention deficit disorder
Age Group: 18-44 years
Sex: M+F
Population Size: 18
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Preferential increases in nucleus accumbens dopamine after systemic cocaine administration are caused by unique characteristics of dopamine neurotransmission.
2001 Aug 15
Effects of sibutramine on the central dopaminergic system in rodents.
2001 Jul
Vitreal dihydroxyphenylacetic acid (DOPAC) as an index of retinal dopamine release.
2001 Mar
Nomifensine-induced c-fos mRNA expression in discrete brain areas of the developing rat.
2001 May 4
Differential time-course profiles of dopamine release and uptake changes induced by three dopamine uptake inhibitors.
2001 Sep 15
Pharmacological characterisation of (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane (PE2I) binding to the rat neuronal dopamine transporter expressed in COS cells.
2002 Feb
Ethanol-induced, nonexocytotic [3H]dopamine release from rat nucleus accumbens slices.
2002 Jun
Characterization of butyrylcholinesterase antagonism of cocaine-induced hyperactivity.
2002 Jun
Characterization of nicotinic agonist-induced [(3)H]dopamine release from synaptosomes prepared from four mouse brain regions.
2002 May
GBR-12909 effect on dopamine outflow depends on phosphorylation in the caudate nucleus of the rat.
2002 Nov
FR143166 attenuates spinal pain transmission through activation of the serotonergic system.
2002 Oct 11
Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes.
2003 Aug
Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells.
2003 Aug 1
Mechanism by which brain-derived neurotrophic factor increases dopamine release from the rabbit retina.
2003 Feb
High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats.
2003 May
(-)-Deprenyl inhibits tyramine-induced noradrenaline release, but not tyramine-induced dopamine release or potassium-induced noradrenaline release, from rat brain synaptosomes.
2004 Mar
[Dopaminergic regulation of theta activity of septohippocampal neuron in the awake rabbit].
2004 Mar-Apr
Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo?
2004 May 7
Involvement of dopamine receptors in the anti-immobility effects of dopamine re-uptake inhibitors in the forced swimming test.
2004 Nov 19
Voltammetric study of the control of striatal dopamine release by glutamate.
2004 Oct
Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation.
2004 Oct
Inhibitory effect of nitric oxide on dopamine transporters: interneuronal communication without receptors.
2004 Sep
Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis.
2005 Jun
Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra.
2005 Mar
Patents

Patents

Sample Use Guides

100 mg at night
Route of Administration: Oral
In Vitro Use Guide
The effect of nomifensine on the uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) into human platelet-rich plasma has been studied. A significant inhibition of DA uptake was observed at nomifensine 10(-6) M. 5-HT uptake was significantly inhibited only at nomifensine 10(-4) M or more. It was concluded, that the human platelet may be used as a model for studying DA uptake as well as that of 5-HT.
Substance Class Chemical
Created
by admin
on Thu Jul 06 11:56:30 UTC 2023
Edited
by admin
on Thu Jul 06 11:56:30 UTC 2023
Record UNII
1LGS5JRP31
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NOMIFENSINE
HSDB   INN   MI   WHO-DD  
INN  
Official Name English
1,2,3,4-TETRAHYDRO-2-METHYL-4-PHENYL-8-ISOQUINOLINAMINE
Systematic Name English
2-METHYL-4-PHENYL-1,2,3,4-TETRAHYDROISOQUINOLIN-8-YLAMINE
Systematic Name English
NOMIFENSINE [MI]
Common Name English
NOMIFENSINE [HSDB]
Common Name English
8-ISOQUINOLINAMINE, 1,2,3,4-TETRAHYDRO-2-METHYL-4-PHENYL-
Systematic Name English
(±)-NOMIFENSINE
Common Name English
LINAMIPHEN
Common Name English
NOMIFENSIN
Brand Name English
(±)-NOMIFENSIN
Common Name English
nomifensine [INN]
Common Name English
Nomifensine [WHO-DD]
Common Name English
ISOQUINOLINE, 8-AMINO-1,2,3,4-TETRAHYDRO-2-METHYL-4-PHENYL-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C265
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
EPA PESTICIDE CODE 600075
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
WHO-VATC QN06AX04
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
WHO-ATC N06AX04
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL273575
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
FDA UNII
1LGS5JRP31
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
EPA CompTox
DTXSID0023377
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
CHEBI
116225
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
DRUG BANK
DB04821
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
INN
2920
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
WIKIPEDIA
NOMIFENSINE
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
DRUG CENTRAL
1958
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
MESH
D009627
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
EVMPD
SUB09347MIG
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
NCI_THESAURUS
C72824
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
HSDB
7702
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
RXCUI
7500
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY RxNorm
PUBCHEM
4528
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
CAS
24526-64-5
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
MERCK INDEX
M8030
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY Merck Index
IUPHAR
4792
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
SMS_ID
100000083568
Created by admin on Thu Jul 06 11:56:31 UTC 2023 , Edited by admin on Thu Jul 06 11:56:31 UTC 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
Related Record Type Details
METABOLITE -> PARENT
IN VITRO
METABOLITE -> PARENT
IN VITRO
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY