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

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
Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation.
2001
[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
The noradrenaline-dopamine interaction in the rat medial prefrontal cortex studied by multi-probe microdialysis.
2001 Apr 27
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
Sub-second changes in accumbal dopamine during sexual behavior in male rats.
2001 Aug 8
Halothane decreases impulse-dependent but not cytoplasmic release of dopamine from rat striatal slices.
2001 Dec
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
Pharmacological characterization and visualization of the glial serotonin transporter.
2001 Jul
Halothane potentiates the effect of methamphetamine and nomifensine on extracellular dopamine levels in rat striatum: a microdialysis study.
2001 Jun
Methyl-4-phenylpyridinium (MPP(+))-evoked dopamine release from rat striatal slices: possible roles of voltage-dependent calcium channels and reverse dopamine transport.
2001 Sep
Differential time-course profiles of dopamine release and uptake changes induced by three dopamine uptake inhibitors.
2001 Sep 15
Mechanism of action of methylmercury on in vivo striatal dopamine release. Possible involvement of dopamine transporter.
2002 Apr
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
Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats.
2002 Jan-Feb
GBR-12909 effect on dopamine outflow depends on phosphorylation in the caudate nucleus of the rat.
2002 Nov
In vivo temporal sequence of rat striatal glutamate, aspartate and dopamine efflux during apomorphine, nomifensine, NMDA and PDC in situ administration.
2002 Oct
Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells.
2003 Aug 1
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
[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
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
Opioid and monoamine systems mediate the discriminative stimulus of tramadol in rats.
2004 Sep 13
Antidepressant-like effect of D(2/3) receptor-, but not D(4) receptor-activation in the rat forced swim test.
2005 Jul
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 Dec 16 19:53:43 UTC 2022
Edited
by admin
on Fri Dec 16 19:53:43 UTC 2022
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 Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
Code System Code Type Description
NSC
289114
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
ChEMBL
CHEMBL273575
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
ECHA (EC/EINECS)
251-223-7
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
MERCK INDEX
M8030
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY Merck Index
RXCUI
262302
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY RxNorm
CAS
32795-47-4
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
PUBCHEM
5358907
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
NCI_THESAURUS
C73808
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
DRUG BANK
DBSALT002854
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
EPA CompTox
DTXSID1045790
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
EVMPD
SUB14663MIG
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
FDA UNII
76S8CUH5MR
Created by admin on Fri Dec 16 19:53:43 UTC 2022 , Edited by admin on Fri Dec 16 19:53:43 UTC 2022
PRIMARY
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