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 8297	4.7 nM [Ki]
dopamine uptake 14 Target ID: GO:0090494 Sources: https://www.ncbi.nlm.nih.gov/pubmed/844493	Inhibitor 8297	26.0 nM [Ki]
serotonin uptake 20 Target ID: GO:0051610 Sources: https://www.ncbi.nlm.nih.gov/pubmed/844493	Inhibitor 8297	4.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3907935	Primary		Withdrawn	Unknown Approved Use Unknown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
A comparison of the patterns of striatal Fos-like immunoreactivity induced by various dopamine agonists in rats.	2000 Aug 4	10904129
Changes in seizure susceptibility to local anesthetics by repeated administration of cocaine and nomifensine but not GBR12935: possible involvement of noradrenergic system.	2000 Jul	10952077
Copper neurotoxicity is dependent on dopamine-mediated copper uptake and one-electron reduction of aminochrome in a rat substantia nigra neuronal cell line.	2001 Apr	11299314
Preferential increases in nucleus accumbens dopamine after systemic cocaine administration are caused by unique characteristics of dopamine neurotransmission.	2001 Aug 15	11487657
Halothane decreases impulse-dependent but not cytoplasmic release of dopamine from rat striatal slices.	2001 Dec	11786236
Halothane potentiates the effect of methamphetamine and nomifensine on extracellular dopamine levels in rat striatum: a microdialysis study.	2001 Jun	11573593
Differential time-course profiles of dopamine release and uptake changes induced by three dopamine uptake inhibitors.	2001 Sep 15	11494401
NMDA antagonist effects on striatal dopamine release: microdialysis studies in awake monkeys.	2002 Jan	11746729
Kinetic analysis of striatal clearance of exogenous dopamine recorded by chronoamperometry in freely-moving rats.	2002 Nov 15	12393160
Role of cerebral dopamine but not plasma insulin, leptin and glucocorticoid in the development of tolerance to the anorectic effect of amphetamine.	2002 Sep	12204294
A role for presynaptic mechanisms in the actions of nomifensine and haloperidol.	2003	12710989
Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes.	2003 Aug	12740868
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	12885429
Strain-dependent modification of behavior following antidepressant treatment.	2003 Feb	12551720
Nomifensine amplifies subsecond dopamine signals in the ventral striatum of freely-moving rats.	2004 Aug	15287895
Dopamine release evoked by beta scorpion toxin, tityus gamma, in prefrontal cortical slices is mediated by intracellular calcium stores.	2004 Dec	15672678
Sibutramine induces potential-dependent exocytotic release but not carrier-mediated release of dopamine and 5-hydroxytryptamine.	2004 Jan 26	14744605
[Effects of anxiolytic drugs on rewarding and aversive behaviors induced by intracranial stimulation].	2004 Jun	15291239
Voltammetric study of the control of striatal dopamine release by glutamate.	2004 Oct	15379902
Inhibitory effect of nitric oxide on dopamine transporters: interneuronal communication without receptors.	2004 Sep	15186914
D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea.	2005	15837140
Dopamine transporter function differences between male and female CD-1 mice.	2005 Feb 28	15722058
Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis.	2005 Jun	15863240
Nicotine and epibatidine alter differently nomifensine-elevated dopamine output in the rat dorsal and ventral striatum.	2005 Mar 28	15792782

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 `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

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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