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
A comparison of the patterns of striatal Fos-like immunoreactivity induced by various dopamine agonists in rats.
2000 Aug 4
[3H]acetycholine release in rat striatal slices is not subject to dopamine heteroreceptor supersensitivity 30 months after 6-hydroxydopamine lesion of the substantia nigra.
2001 Apr
A method to evaluate the diffusion rate of drugs from a microdialysis probe through brain tissue.
2001 Aug 15
Preferential increases in nucleus accumbens dopamine after systemic cocaine administration are caused by unique characteristics of dopamine neurotransmission.
2001 Aug 15
Halothane decreases impulse-dependent but not cytoplasmic release of dopamine from rat striatal slices.
2001 Dec
Dopamine transporter binding in the rat striatum is increased by gestational, perinatal, and adolescent exposure to heptachlor.
2001 Dec
Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo.
2001 Dec 15
Activation of the dopaminergic system of medial prefrontal cortex of gerbils during formation of relevant associations for the avoidance strategy in the shuttle-box.
2001 Feb
Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity.
2001 Feb 23
Effects of sibutramine on the central dopaminergic system in rodents.
2001 Jul
Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome c and caspases.
2001 Jul
Halothane potentiates the effect of methamphetamine and nomifensine on extracellular dopamine levels in rat striatum: a microdialysis study.
2001 Jun
Accumbens dopamine mechanisms in sucrose intake.
2001 Jun 15
Differential sensitivity to NaCl for inhibitors and substrates that recognize mutually exclusive binding sites on the neuronal transporter of dopamine in rat striatal membranes.
2001 Mar
Modulation of dopamine uptake in rat nucleus accumbens: effect of specific dopamine receptor antagonists and sigma ligands.
2001 Oct 26
Differential time-course profiles of dopamine release and uptake changes induced by three dopamine uptake inhibitors.
2001 Sep 15
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
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
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
Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats.
2002 Jan-Feb
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
Kinetic analysis of striatal clearance of exogenous dopamine recorded by chronoamperometry in freely-moving rats.
2002 Nov 15
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
A role for presynaptic mechanisms in the actions of nomifensine and haloperidol.
2003
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
Functionally distinct dopamine and octopamine transporters in the CNS of the cabbage looper moth.
2003 Feb
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
Mechanisms underlying domoic acid-induced dopamine release from striatum: an in vivo microdialysis study.
2003 Oct
Sibutramine induces potential-dependent exocytotic release but not carrier-mediated release of dopamine and 5-hydroxytryptamine.
2004 Jan 26
Methylphenidate restores ventral tegmental area dopamine neuron activity in prenatal ethanol-exposed rats by augmenting dopamine neurotransmission.
2004 May
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 transporter function differences between male and female CD-1 mice.
2005 Feb 28
Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis.
2005 Jun
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 Sat Dec 16 06:18:33 GMT 2023
Edited
by admin
on Sat Dec 16 06:18:33 GMT 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 Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
EPA PESTICIDE CODE 600075
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
WHO-VATC QN06AX04
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
WHO-ATC N06AX04
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL273575
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
FDA UNII
1LGS5JRP31
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
EPA CompTox
DTXSID0023377
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
CHEBI
116225
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
DRUG BANK
DB04821
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
INN
2920
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
WIKIPEDIA
NOMIFENSINE
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
DRUG CENTRAL
1958
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
MESH
D009627
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
EVMPD
SUB09347MIG
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
NCI_THESAURUS
C72824
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
HSDB
7702
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
RXCUI
7500
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY RxNorm
PUBCHEM
4528
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
CAS
24526-64-5
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
MERCK INDEX
m8030
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY Merck Index
IUPHAR
4792
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
SMS_ID
100000083568
Created by admin on Sat Dec 16 06:18:34 GMT 2023 , Edited by admin on Sat Dec 16 06:18:34 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
Due to a risk of haemolytic anaemia, the U.S. Food and Drug Administration (FDA) withdrew approval for nomifensine on March 20, 1992. Nomifensine was subsequently withdrawn from the Canadian and UK markets as well.
BINDING
IC50
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