Nomifensine

Identification

Name

Nomifensine

Accession Number

DB04821

Description

Nomifensine, formerly marketed as Merital capsules, was associated with an increased incidence of hemolytic anemia. The approved application holder removed Merital capsules from the market on January 23, 1986. FDA published a notice of its determination that Merital capsules were removed from the market for safety reasons (see the Federal Register of June 17, 1986 (51 FR 21981)). Approval of the NDA for Merital capsules was withdrawn on March 20, 1992 (see the Federal Register of March 20, 1992 (57 FR 9729)). Also withdrawn from the Canadian and UK markets.

Type

Small Molecule

Groups

Approved, Withdrawn

Structure

Similar Structures

Weight: Average: 238.3275
Monoisotopic: 238.146998586
Chemical Formula: C₁₆H₁₈N₂

Synonyms

(+-)-nomifensin
(+-)-nomifensine
2-Methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine
8-Amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline
D,L-nomifensine
Nomifensin
Nomifensina
Nomifensine
Nomifensinum

Pharmacology

Indication

Not Available

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

Nomifensine is a dopamine reuptake inhibitor test-marketed in the United States by Hoechst AG (now Novartis) that increases the amount of synaptic dopamine available to receptors by blocking dopamine's re-uptake transporter. Nomifensine is now mainly used in scientific research, particularly in studies involving dopamine release in response to addiction.

Mechanism of action

Target	Actions	Organism
USodium-dependent noradrenaline transporter	Not Available	Humans
USodium-dependent dopamine transporter	Not Available	Humans
UAmine oxidase [flavin-containing] B	Not Available	Humans
UAmine oxidase [flavin-containing] A	Not Available	Humans
UMyeloperoxidase	Not Available	Humans
USodium-dependent serotonin transporter	Not Available	Humans
USynaptic vesicular amine transporter	Not Available	Humans

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

A likely cause of nomifensine toxicity is the aromatic amine group, as compounds containing this chemical substructure are notorious for producing toxic metabolites.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Unlock Additional Data
Acenocoumarol	The risk or severity of adverse effects can be increased when Nomifensine is combined with Acenocoumarol.
Acetazolamide	The risk or severity of adverse effects can be increased when Acetazolamide is combined with Nomifensine.
Acetophenazine	The risk or severity of adverse effects can be increased when Acetophenazine is combined with Nomifensine.
Aclidinium	Nomifensine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
Agomelatine	The risk or severity of adverse effects can be increased when Nomifensine is combined with Agomelatine.
Alfentanil	The risk or severity of adverse effects can be increased when Alfentanil is combined with Nomifensine.
Alimemazine	The risk or severity of adverse effects can be increased when Alimemazine is combined with Nomifensine.
Almotriptan	The risk or severity of adverse effects can be increased when Almotriptan is combined with Nomifensine.
Alosetron	The risk or severity of adverse effects can be increased when Alosetron is combined with Nomifensine.
Alprazolam	The risk or severity of adverse effects can be increased when Alprazolam is combined with Nomifensine.

Additional Data Available

Extended Description

Available for Purchase

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

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A severity rating for each drug interaction, from minor to major.

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Evidence Level

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A rating for the strength of the evidence supporting each drug interaction.

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Action

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An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Nomifensine maleate	76S8CUH5MR	32795-47-4	GEOCVSMCLVIOEV-BTJKTKAUSA-N

International/Other Brands

Linamiphen

Chemical Identifiers

UNII: 1LGS5JRP31
CAS number: 24526-64-5
InChI Key: XXPANQJNYNUNES-UHFFFAOYSA-N
InChI: 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
IUPAC Name: 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-amine
SMILES: CN1CC(C2=CC=CC=C2)C2=C(C1)C(N)=CC=C2

References

Synthesis Reference

US3577424

General References

Not Available

External Links

PubChem Compound: 4528
PubChem Substance: 46505804
ChemSpider: 4371
BindingDB: 50005548
RxNav: 7500
ChEBI: 116225
ChEMBL: CHEMBL273575
Therapeutic Targets Database: DCL000339
Wikipedia: Nomifensine

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count

Pharmacoeconomics

Manufacturers: Not Available
Packagers: Not Available
Dosage Forms: Not Available
Prices: Not Available
Patents: Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	180 °C	PhysProp

Predicted Properties

Property	Value	Source
Water Solubility	0.318 mg/mL	ALOGPS
logP	2.94	ALOGPS
logP	2.62	ChemAxon
logS	-2.9	ALOGPS
pKa (Strongest Basic)	8.88	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	29.26 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	77.18 m³·mol^-1	ChemAxon
Polarizability	27.56 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9837
Caco-2 permeable	+	0.7206
P-glycoprotein substrate	Substrate	0.5814
P-glycoprotein inhibitor I	Non-inhibitor	0.8827
P-glycoprotein inhibitor II	Non-inhibitor	0.6448
Renal organic cation transporter	Non-inhibitor	0.5406
CYP450 2C9 substrate	Non-substrate	0.8614
CYP450 2D6 substrate	Non-substrate	0.545
CYP450 3A4 substrate	Non-substrate	0.5637
CYP450 1A2 substrate	Inhibitor	0.9106
CYP450 2C9 inhibitor	Non-inhibitor	0.9404
CYP450 2D6 inhibitor	Inhibitor	0.8932
CYP450 2C19 inhibitor	Non-inhibitor	0.9026
CYP450 3A4 inhibitor	Non-inhibitor	0.8309
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.6612
Ames test	Non AMES toxic	0.9133
Carcinogenicity	Non-carcinogens	0.9183
Biodegradation	Not ready biodegradable	0.9692
Rat acute toxicity	2.9821 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9534
hERG inhibition (predictor II)	Inhibitor	0.7539

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	1200	N/A	N/A
Ki (nM)	15.6	N/A	N/A	9537821
Ki (nM)	23	N/A	N/A	23084899
Ki (nM)	29	N/A	N/A	12431845
Ki (nM)	4	N/A	N/A
Ki (nM)	5	N/A	N/A

Details1. Sodium-dependent noradrenaline transporter

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Norepinephrine:sodium symporter activity
Specific Function: Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name: SLC6A2
Uniprot ID: P23975
Uniprot Name: Sodium-dependent noradrenaline transporter
Molecular Weight: 69331.42 Da

References

Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	30.2	N/A	N/A	21093273
Ki (nM)	10	N/A	N/A
Ki (nM)	23.5	N/A	N/A
Ki (nM)	40.2	N/A	N/A	8302271
Ki (nM)	42	N/A	N/A	8302271
Ki (nM)	450	N/A	N/A
Ki (nM)	53	N/A	N/A	8302271 / 12431845
Ki (nM)	56	N/A	N/A	9537821
Ki (nM)	56.4	N/A	N/A	8302271
Ki (nM)	7	N/A	N/A
Ki (nM)	84	N/A	N/A	23084899

Details2. Sodium-dependent dopamine transporter

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Monoamine transmembrane transporter activity
Specific Function: Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name: SLC6A3
Uniprot ID: Q01959
Uniprot Name: Sodium-dependent dopamine transporter
Molecular Weight: 68494.255 Da

References

Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]

Details3. Amine oxidase [flavin-containing] B

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Primary amine oxidase activity
Specific Function: Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name: MAOB
Uniprot ID: P27338
Uniprot Name: Amine oxidase [flavin-containing] B
Molecular Weight: 58762.475 Da

References

Egashira T, Takayama F, Yamanaka Y: The inhibition of monoamine oxidase activity by various antidepressants: differences found in various mammalian species. Jpn J Pharmacol. 1999 Sep;81(1):115-21. [PubMed:10580379]

Details4. Amine oxidase [flavin-containing] A

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Serotonin binding
Specific Function: Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name: MAOA
Uniprot ID: P21397
Uniprot Name: Amine oxidase [flavin-containing] A
Molecular Weight: 59681.27 Da

References

Egashira T, Takayama F, Yamanaka Y: The inhibition of monoamine oxidase activity by various antidepressants: differences found in various mammalian species. Jpn J Pharmacol. 1999 Sep;81(1):115-21. [PubMed:10580379]

Details5. Myeloperoxidase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Peroxidase activity
Specific Function: Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
Gene Name: MPO
Uniprot ID: P05164
Uniprot Name: Myeloperoxidase
Molecular Weight: 83867.71 Da

References

Obach RS, Dalvie DK: Metabolism of nomifensine to a dihydroisoquinolinium ion metabolite by human myeloperoxidase, hemoglobin, monoamine oxidase A, and cytochrome P450 enzymes. Drug Metab Dispos. 2006 Aug;34(8):1310-6. Epub 2006 May 5. [PubMed:16679384]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	1010	N/A	N/A	9537821
Ki (nM)	1200	N/A	N/A
Ki (nM)	1400	N/A	N/A
Ki (nM)	2057	N/A	N/A	23084899
Ki (nM)	4872	N/A	N/A	12431845
Ki (nM)	800	N/A	N/A

Details6. Sodium-dependent serotonin transporter

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Serotonin:sodium symporter activity
Specific Function: Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name: SLC6A4
Uniprot ID: P31645
Uniprot Name: Sodium-dependent serotonin transporter
Molecular Weight: 70324.165 Da

References

Henry LK, Field JR, Adkins EM, Parnas ML, Vaughan RA, Zou MF, Newman AH, Blakely RD: Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants. J Biol Chem. 2006 Jan 27;281(4):2012-23. Epub 2005 Nov 3. [PubMed:16272152]

Details7. Synaptic vesicular amine transporter

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Monoamine transmembrane transporter activity
Specific Function: Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles...
Gene Name: SLC18A2
Uniprot ID: Q05940
Uniprot Name: Synaptic vesicular amine transporter
Molecular Weight: 55712.075 Da

References

Gonzalez AM, Walther D, Pazos A, Uhl GR: Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. [PubMed:7912402]

Carriers

Details1. Alpha-1-acid glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: No

General Function: Not Available
Specific Function: Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name: ORM1
Uniprot ID: P02763
Uniprot Name: Alpha-1-acid glycoprotein 1
Molecular Weight: 23511.38 Da

References

Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208. [PubMed:2870173]

Drug created on September 11, 2007 14:22 / Updated on June 12, 2020 10:52

Nomifensine

Identification

Structure for Nomifensine (DB04821)

Pharmacology

Learn about our commercial Contraindications & Blackbox Warnings data.

Learn about our commercial Adverse Effects data.

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References

References

References

References

References

References

References

Carriers

References