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Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3907935	Primary		Withdrawn	Unknown Approved Use Unknown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
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
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
Characterization of the analgesic properties of nomifensine in rats.	2001 Apr	11526977
[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
Sub-second changes in accumbal dopamine during sexual behavior in male rats.	2001 Aug 8	11496146
Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity.	2001 Feb 23	11263672
Plasticity in serotonin uptake in primary neuronal cultures of serotonin transporter knockout mice.	2001 Jan 31	11172895
Effects of sibutramine on the central dopaminergic system in rodents.	2001 Jul	15111248
Accumbens dopamine mechanisms in sucrose intake.	2001 Jun 15	11516413
Modulation of dopamine uptake in rat nucleus accumbens: effect of specific dopamine receptor antagonists and sigma ligands.	2001 Oct 26	11602337
Phencyclidine-induced dysregulation of dopamine response to amphetamine in prefrontal cortex and striatum.	2001 Sep	11699927
Mechanism of action of methylmercury on in vivo striatal dopamine release. Possible involvement of dopamine transporter.	2002 Apr	11821154
In vivo evidence for a lack of central effect of ebastine, an antihistaminic agent, in rats: a microdialysis study.	2002 Dec	12501012
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
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
Characterization of nicotinic agonist-induced [(3)H]dopamine release from synaptosomes prepared from four mouse brain regions.	2002 May	11961070
GBR-12909 effect on dopamine outflow depends on phosphorylation in the caudate nucleus of the rat.	2002 Nov	12211084
Aged Fischer 344 rats exhibit altered locomotion in the absence of decreased locomotor activity: exacerbation by nomifensine.	2002 Nov 29	12429381
FR143166 attenuates spinal pain transmission through activation of the serotonergic system.	2002 Oct 11	12359273
Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells.	2003 Aug 1	12868068
Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.	2003 May	12878270
Mechanisms underlying domoic acid-induced dopamine release from striatum: an in vivo microdialysis study.	2003 Oct	14570393
Involvement of dopamine receptors in the anti-immobility effects of dopamine re-uptake inhibitors in the forced swimming test.	2004 Nov 19	15541423
Voltammetric study of the control of striatal dopamine release by glutamate.	2004 Oct	15379902
Opioid and monoamine systems mediate the discriminative stimulus of tramadol in rats.	2004 Sep 13	15363988
Dopamine transporter function differences between male and female CD-1 mice.	2005 Feb 28	15722058
Antidepressant-like effect of D(2/3) receptor-, but not D(4) receptor-activation in the rat forced swim test.	2005 Jul	15688083

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