NOMIFENSINE

US Previously Marketed

First approved in 1984

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 Search

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	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/844493 | https://www.ncbi.nlm.nih.gov/pubmed/20742679

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
norepinephrine uptake 18 Target ID: GO:0051620 Sources: https://www.ncbi.nlm.nih.gov/pubmed/844493	Inhibitor 8228	4.7 nM [Ki]
dopamine uptake 14 Target ID: GO:0090494 Sources: https://www.ncbi.nlm.nih.gov/pubmed/844493	Inhibitor 8228	26.0 nM [Ki]
serotonin uptake 20 Target ID: GO:0051610 Sources: https://www.ncbi.nlm.nih.gov/pubmed/844493	Inhibitor 8228	4.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3907935	Primary		Withdrawn	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
84 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7082545	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/7049645	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

Value	Dose	Co-administered	Analyte	Population
196.8 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7082545	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7082545	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/7049645	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
25% REVIEW https://pubmed.ncbi.nlm.nih.gov/7049645	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/2651559	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: https://pubmed.ncbi.nlm.nih.gov/2651559	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: https://pubmed.ncbi.nlm.nih.gov/2651559
100 mg single, intravenous Dose: 100 mg Route: intravenous Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3956054	healthy, 22-41 years Health Status: healthy Age Group: 22-41 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3956054	Sources: https://pubmed.ncbi.nlm.nih.gov/3956054

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/2651559	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: https://pubmed.ncbi.nlm.nih.gov/2651559
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: https://pubmed.ncbi.nlm.nih.gov/2651559	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: https://pubmed.ncbi.nlm.nih.gov/2651559
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: https://pubmed.ncbi.nlm.nih.gov/2651559	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: https://pubmed.ncbi.nlm.nih.gov/2651559

Sourcing

Vendor/Aggregator	ID	URL
AHH Chemical co.,ltd	MT-57174	http://www.ahhchemical.com/product/MT-57174.html
AK Scientific, Inc. (AKSCI)	2594AH	http://www.aksci.com/item_detail.php?cat=2594AH
AbMole Bioscience	M2886	http://www.abmole.com/products/nomifensine-maleate.html
Achemtek	0104-021588	http://www.achemtek.com/32795-47-4
Ambeed	A428762	https://www.ambeed.com/products/32795-47-4.html
Ambinter	Amb10843762	http://www.ambinter.com/reference/10843762
Aurora Fine Chemicals LLC	A17.880.045	http://online.aurorafinechemicals.com/info?ID=A17.880.045
BLD Pharm	BD145381	http://www.bldpharm.com/products/32795-47-4.html
BioCrick	BCC7226	http://www.biocrick.com/Nomifensine-BCC7226.html
BioSynth	J-018882	https://www.biosynth.com/en/products/all-products/products/J-018882.html
Chem Scene	CS-4709	http://www.chemscene.com/32795-47-4.html
Excenen	EX-A3993	https://www.excenen.com/searchresultlist.php?id=EX-A3993
LGC Standards	LGCFOR3158.00	https://www.lgcstandards.com/US/en/p/LGCFOR3158.00
Lab Network	LN01306593	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01306593
MedChem Express	HY-B1110A	https://www.medchemexpress.com/Nomifensine-maleate.html
MolPort	MolPort-003-666-476	https://www.molport.com/shop/molecule-link/MolPort-003-666-476
Sigma-Aldrich	N1530_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/n1530?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S537458	http://www.smolecule.com/products/s537458
THE BioTek	bt-277462	https://www.thebiotek.com/product/inhibitors/bt-277462
eNovation Chemicals	D671289	https://www.enovationchem.com/ProductDetails.asp?ProductID=D671289
iChemical	EBD3055579	http://www.ichemical.com/products/32795-47-4.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
On the anticataleptic action of cyproheptadine.	1976 Aug	1033567
A comparison of the patterns of striatal Fos-like immunoreactivity induced by various dopamine agonists in rats.	2000 Aug 4	10904129
[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	11330335
Effects of sibutramine on the central dopaminergic system in rodents.	2001 Jul	15111248
Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome c and caspases.	2001 Jul	11461973
The emergence test: effects of psychotropic drugs on neophobic disposition in Wistar Kyoto (WKY) and Sprague Dawley rats.	2001 Nov	11642658
Phencyclidine-induced dysregulation of dopamine response to amphetamine in prefrontal cortex and striatum.	2001 Sep	11699927
Semicarbazide-sensitive amine oxidase (SSAO) in the brain.	2002 Apr	11958526
The spinal antinociceptive effect of kyotorphin in mice: involvement of the descending noradrenergic and serotonergic systems.	2002 Aug 30	12165410
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	12438514
NMDA antagonist effects on striatal dopamine release: microdialysis studies in awake monkeys.	2002 Jan	11746729
Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats.	2002 Jan-Feb	11812540
The selective serotonin reuptake inhibitor citalopram induces the storage of serotonin in catecholaminergic terminals.	2002 Jul	12065714
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	12162539
Ethanol-induced, nonexocytotic [3H]dopamine release from rat nucleus accumbens slices.	2002 Jun	12106832
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	11927365
Characterization of nicotinic agonist-induced [(3)H]dopamine release from synaptosomes prepared from four mouse brain regions.	2002 May	11961070
Selective blockade of drug-induced place preference conditioning by ACPC, a functional NDMA-receptor antagonist.	2002 Nov	12431848
Kinetic analysis of striatal clearance of exogenous dopamine recorded by chronoamperometry in freely-moving rats.	2002 Nov 15	12393160
In vivo temporal sequence of rat striatal glutamate, aspartate and dopamine efflux during apomorphine, nomifensine, NMDA and PDC in situ administration.	2002 Oct	12384168
Modification of the striatal dopaminergic neuron system by carbon monoxide exposure in free-moving rats, as determined by in vivo brain microdialysis.	2002 Oct	12373456
Aged Fischer 344 rats exhibit altered orolingual motor function: relationships with nigrostriatal neurochemical measures.	2003 Mar-Apr	12498959
Nomifensine amplifies subsecond dopamine signals in the ventral striatum of freely-moving rats.	2004 Aug	15287895
Prenatal cocaine exposure decreases nigrostriatal dopamine release in vitro: effects of age and sex.	2004 Aug	15170820
Uptake inhibitors but not substrates induce protease resistance in extracellular loop two of the dopamine transporter.	2004 Mar	14978248
(-)-Deprenyl inhibits tyramine-induced noradrenaline release, but not tyramine-induced dopamine release or potassium-induced noradrenaline release, from rat brain synaptosomes.	2004 Mar	14726221
[Dopaminergic regulation of theta activity of septohippocampal neuron in the awake rabbit].	2004 Mar-Apr	15174266
Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation.	2004 Oct	15163680
Inhibitory effect of nitric oxide on dopamine transporters: interneuronal communication without receptors.	2004 Sep	15186914
Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis.	2005 Jun	15863240

Patents

Sample Use Guides

In Vivo Use Guide

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

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