Nomifensine
Identification
- Generic Name
- Nomifensine
- DrugBank Accession Number
- DB04821
- Background
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 Approval of the NDA for Merital capsules was withdrawn on March 20, 1992 (see the Federal Register of March 20, 1992 (57 FR 9729)). Also withdrawn from the Canadian and UK markets.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- Approved, Withdrawn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
Structure for Nomifensine (DB04821)
- 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
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
A likely cause of nomifensine toxicity is the aromatic amine group, as compounds containing this chemical substructure are notorious for producing toxic metabolites.
- 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 Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Nomifensine is combined with 1,2-Benzodiazepine. 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. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Nomifensine maleate 76S8CUH5MR 32795-47-4 GEOCVSMCLVIOEV-BTJKTKAUSA-N - International/Other Brands
- Linamiphen
Categories
- ATC Codes
- N06AX04 — Nomifensine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 4-phenyltetrahydroisoquinolines. These are compounds containing a phenyl group attached to the C4-atom of a tetrahydroisoquinoline moiety.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Tetrahydroisoquinolines
- Sub Class
- 4-phenyltetrahydroisoquinolines
- Direct Parent
- 4-phenyltetrahydroisoquinolines
- Alternative Parents
- Aminoquinolines and derivatives / Aralkylamines / Benzene and substituted derivatives / Trialkylamines / Azacyclic compounds / Primary amines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 4-phenyltetrahydroisoquinoline / Amine / Aminoquinoline / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- isoquinolines (CHEBI:116225)
- Affected organisms
- Humans and other mammals
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
- 7500
- ChEBI
- 116225
- ChEMBL
- CHEMBL273575
- Therapeutic Targets Database
- DCL000339
- Wikipedia
- Nomifensine
Clinical Trials
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
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
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- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Carriers
- 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. [Article]
Drug created on September 11, 2007 20:22 / Updated on February 21, 2021 18:51