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

Details

Stereochemistry RACEMIC
Molecular Formula C16H18N2
Molecular Weight 238.3281
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NOMIFENSINE

SMILES

CN1CC(c2ccccc2)c3cccc(c3C1)N

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 238.3281
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
Effects of sibutramine on the central dopaminergic system in rodents.
2001 Jul
Semicarbazide-sensitive amine oxidase (SSAO) in the brain.
2002 Apr
Mechanism of action of methylmercury on in vivo striatal dopamine release. Possible involvement of dopamine transporter.
2002 Apr
The spinal antinociceptive effect of kyotorphin in mice: involvement of the descending noradrenergic and serotonergic systems.
2002 Aug 30
In vivo evidence for a lack of central effect of ebastine, an antihistaminic agent, in rats: a microdialysis study.
2002 Dec
Destruction of serotonergic nerve terminals prevents fluoxetine-induced desensitization of hypothalamic 5-HT(1A) receptors.
2002 Dec
Dopamine, but not norepinephrine or serotonin, reuptake inhibition reverses motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates.
2002 Dec
3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (trp-P-1) is incorporated into rat splenocytes, thymocytes, and hepatocytes through monoamine transporters and induces apoptosis.
2002 Jun
Ethanol-induced, nonexocytotic [3H]dopamine release from rat nucleus accumbens slices.
2002 Jun
NMDA and AMPA/kainate glutamatergic agonists increase the extracellular concentrations of GABA in the prefrontal cortex of the freely moving rat: modulation by endogenous dopamine.
2002 Mar 15
Effects of catecholamine uptake blockers in the caudate-putamen and subregions of the medial prefrontal cortex of the rat.
2002 May 17
Selective blockade of drug-induced place preference conditioning by ACPC, a functional NDMA-receptor antagonist.
2002 Nov
GBR-12909 effect on dopamine outflow depends on phosphorylation in the caudate nucleus of the rat.
2002 Nov
Kinetic analysis of striatal clearance of exogenous dopamine recorded by chronoamperometry in freely-moving rats.
2002 Nov 15
Aged Fischer 344 rats exhibit altered locomotion in the absence of decreased locomotor activity: exacerbation by nomifensine.
2002 Nov 29
In vivo temporal sequence of rat striatal glutamate, aspartate and dopamine efflux during apomorphine, nomifensine, NMDA and PDC in situ administration.
2002 Oct
Modification of the striatal dopaminergic neuron system by carbon monoxide exposure in free-moving rats, as determined by in vivo brain microdialysis.
2002 Oct
FR143166 attenuates spinal pain transmission through activation of the serotonergic system.
2002 Oct 11
Role of cerebral dopamine but not plasma insulin, leptin and glucocorticoid in the development of tolerance to the anorectic effect of amphetamine.
2002 Sep
Bupropion inhibits nicotine-evoked [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine and from rat hippocampal slices preloaded with [(3)H]norepinephrine.
2002 Sep
Altered dopamine release and uptake kinetics in mice lacking D2 receptors.
2002 Sep 15
The effects of systemically administered taurine and N-pivaloyltaurine on striatal extracellular dopamine and taurine in freely moving rats.
2003 Aug
Identification of dopamine transporter in bovine pineal gland using [3H]GBR 12935.
2003 Aug
Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells.
2003 Aug 1
In vitro pharmacological characterization of (+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A), a nicotinic acetylcholine receptor ligand.
2003 Aug 15
Mechanism by which brain-derived neurotrophic factor increases dopamine release from the rabbit retina.
2003 Feb
Strain-dependent modification of behavior following antidepressant treatment.
2003 Feb
Discriminative stimulus effects of (-)-ephedrine in rats: analysis with catecholamine transporter and receptor ligands.
2003 Jun 5
Aged Fischer 344 rats exhibit altered orolingual motor function: relationships with nigrostriatal neurochemical measures.
2003 Mar-Apr
Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.
2003 May
8-[3H]-hydroxy-2-(di-n-propylamino)tetralin binding sites in blood lymphocytes of rats and the modulation by mitogens and immobilization.
2003 May
Mechanisms underlying domoic acid-induced dopamine release from striatum: an in vivo microdialysis study.
2003 Oct
Enhanced attention in rhesus monkeys as a common factor for the cognitive effects of drugs with abuse potential.
2003 Sep
Nomifensine amplifies subsecond dopamine signals in the ventral striatum of freely-moving rats.
2004 Aug
Prenatal cocaine exposure decreases nigrostriatal dopamine release in vitro: effects of age and sex.
2004 Aug
Dopamine release evoked by beta scorpion toxin, tityus gamma, in prefrontal cortical slices is mediated by intracellular calcium stores.
2004 Dec
Sibutramine induces potential-dependent exocytotic release but not carrier-mediated release of dopamine and 5-hydroxytryptamine.
2004 Jan 26
[Effects of anxiolytic drugs on rewarding and aversive behaviors induced by intracranial stimulation].
2004 Jun
Uptake inhibitors but not substrates induce protease resistance in extracellular loop two of the dopamine transporter.
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
Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation.
2004 Oct
Reduced inhibitory action of a GABAB receptor agonist on [3H]-dopamine release from rat ventral tegmental area in vitro after chronic nicotine administration.
2004 Oct 20
Inhibitory effect of nitric oxide on dopamine transporters: interneuronal communication without receptors.
2004 Sep
D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea.
2005
Antidepressant-like effect of D(2/3) receptor-, but not D(4) receptor-activation in the rat forced swim test.
2005 Jul
Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis.
2005 Jun
Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa.
2005 Mar
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 Fri Jun 25 23:49:19 UTC 2021
Edited
by admin
on Fri Jun 25 23:49:19 UTC 2021
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
NOMIFENSINE [WHO-DD]
Common Name English
NOMIFENSIN
Brand Name English
(+/-)-NOMIFENSIN
Common Name English
NOMIFENSINE [INN]
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 Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
EPA PESTICIDE CODE 600075
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
WHO-VATC QN06AX04
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
WHO-ATC N06AX04
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL273575
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
FDA UNII
1LGS5JRP31
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
EPA CompTox
24526-64-5
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
DRUG BANK
DB04821
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
INN
2920
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
WIKIPEDIA
NOMIFENSINE
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
DRUG CENTRAL
1958
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
MESH
D009627
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
EVMPD
SUB09347MIG
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
NCI_THESAURUS
C72824
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
HSDB
7702
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
RXCUI
7500
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY RxNorm
PUBCHEM
4528
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
CAS
24526-64-5
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
MERCK INDEX
M8030
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY Merck Index
IUPHAR
4792
Created by admin on Fri Jun 25 23:49:19 UTC 2021 , Edited by admin on Fri Jun 25 23:49:19 UTC 2021
PRIMARY
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