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

Details

Stereochemistry RACEMIC
Molecular Formula C16H18N2.C4H4O4
Molecular Weight 354.3997
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of NOMIFENSINE MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CN1CC(C2=CC=CC=C2)C3=C(C1)C(N)=CC=C3

InChI

InChIKey=GEOCVSMCLVIOEV-BTJKTKAUSA-N
InChI=1S/C16H18N2.C4H4O4/c1-18-10-14(12-6-3-2-4-7-12)13-8-5-9-16(17)15(13)11-18;5-3(6)1-2-4(7)8/h2-9,14H,10-11,17H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

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 ( + / - )

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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
Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation.
2001
The noradrenaline-dopamine interaction in the rat medial prefrontal cortex studied by multi-probe microdialysis.
2001 Apr 27
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
Determination of release and uptake parameters from electrically evoked dopamine dynamics measured by real-time voltammetry.
2001 Dec 15
Nomifensine reveals age-related changes in K(+)-evoked striatal DA overflow in F344 rats.
2001 May-Jun
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
The spinal antinociceptive effect of FR140423 in mice involvement of the descending noradrenergic and serotonergic systems.
2001 Sep 28
Semicarbazide-sensitive amine oxidase (SSAO) in the brain.
2002 Apr
In vivo evidence for a lack of central effect of ebastine, an antihistaminic agent, in rats: a microdialysis study.
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
The selective serotonin reuptake inhibitor citalopram induces the storage of serotonin in catecholaminergic terminals.
2002 Jul
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
Effects of catecholamine uptake blockers in the caudate-putamen and subregions of the medial prefrontal cortex of the rat.
2002 May 17
FR143166 attenuates spinal pain transmission through activation of the serotonergic system.
2002 Oct 11
A role for presynaptic mechanisms in the actions of nomifensine and haloperidol.
2003
Tetrahydrobiopterin precursor sepiapterin provides protection against neurotoxicity of 1-methyl-4-phenylpyridinium in nigral slice cultures.
2003 Apr
The effects of systemically administered taurine and N-pivaloyltaurine on striatal extracellular dopamine and taurine in freely moving rats.
2003 Aug
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
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
High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats.
2003 May
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
[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
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
Opioid and monoamine systems mediate the discriminative stimulus of tramadol in rats.
2004 Sep 13
D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea.
2005
Dopamine transporter function differences between male and female CD-1 mice.
2005 Feb 28
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
Nicotine and epibatidine alter differently nomifensine-elevated dopamine output in the rat dorsal and ventral striatum.
2005 Mar 28
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 Wed Jul 05 23:46:35 UTC 2023
Edited
by admin
on Wed Jul 05 23:46:35 UTC 2023
Record UNII
76S8CUH5MR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NOMIFENSINE MALEATE
MART.   MI   USAN   WHO-DD  
USAN  
Official Name English
MERITAL
Brand Name English
8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline maleate (1:1)
Systematic Name English
ALIVAL (ANTIDEPRESSANT)
Brand Name English
8-ISOQUINOLINAMINE, 1,2,3,4-TETRAHYDRO-2-METHYL-4-PHENYL-, (Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
NOMIFENSINE MALEATE [MI]
Common Name English
NOMIFENSINE MALEATE [USAN]
Common Name English
NOMIFENSINE MALEATE [MART.]
Common Name English
HOE-984
Code English
PSICRONIZER
Common Name English
NOMIFENSINE HYDROGEN MALEATE
Common Name English
(±)-NOMIFENSINE HYDROGEN MALEATE
Common Name English
8-ISOQUINOLINAMINE, 1,2,3,4-TETRAHYDRO-2-METHYL-4-PHENYL-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
HOE 984
Code English
NSC-289114
Code English
HOSTALIVAL
Common Name English
Nomifensine maleate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C265
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
Code System Code Type Description
NSC
289114
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
SMS_ID
100000080020
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
ChEMBL
CHEMBL273575
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
ECHA (EC/EINECS)
251-223-7
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
MERCK INDEX
M8030
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY Merck Index
RXCUI
262302
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY RxNorm
CAS
32795-47-4
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
PUBCHEM
5358907
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
NCI_THESAURUS
C73808
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
DRUG BANK
DBSALT002854
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
EPA CompTox
DTXSID1045790
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
EVMPD
SUB14663MIG
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
FDA UNII
76S8CUH5MR
Created by admin on Wed Jul 05 23:46:35 UTC 2023 , Edited by admin on Wed Jul 05 23:46:35 UTC 2023
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY