Details of the Drug

General Information of Drug (ID: DMCP2TS)

• Drug Name: Nomifensine
• Synonyms: Linamiphen; Nomifenison; Nomifensin; Nomifensina; Nomifensinum; Nomiphensine; Nomifensina [INN-Spanish]; Nomifensine [INN:BAN]; Nomifensine maleate(USAN); Nomifensinum [INN-Latin]; D,L-nomifensine; Nomifensine Maleate (1:1); R/S-nomifensine; (+)-Nomifensine; (+)-Nomiphensine; (+-)-1,2,3,4-Tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine; (+-)-Nomifensin; (+-)-Nomifensine; (R)-1,2,3,4-Tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine; 2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine; 2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine 2-butenedioate; 2-Methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine; 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-amine; 2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine; 8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisochinolin; 8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline; 8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline maleate (1:1); 8-Amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 8-Isoquinolinamine, 1,2,3,4-tetrahydro-2-methyl-4-phenyl; 8-Isoquinolinamine, 1,2,3,4-tetrahydro-2-methyl-4-phenyl-(9CI)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Withdrawn from market	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 238.33
  Topological Polar Surface Area (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 22 mL/min/kg [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 6.5 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 11.988 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.4% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 6 L/kg [4]
• Chemical Identifiers:
  Formula: C16H18N2
  IUPAC Name: 2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine
  Canonical SMILES: CN1CC(C2=C(C1)C(=CC=C2)N)C3=CC=CC=C3
  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
  InChIKey: XXPANQJNYNUNES-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4528
  ChEBI ID: CHEBI:116225
  CAS Number: 24526-64-5
  DrugBank ID: DB04821
  TTD ID: D06BPG
  VARIDT ID: DR00944

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[6], [7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4792).
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] Pharmacologically induced, subsecond dopamine transients in the caudate-putamen of the anesthetized rat. Synapse. 2007 Jan;61(1):37-9.
• [7] Dopamine D2 receptors: a potential pharmacological target for nomifensine and tranylcypromine but not other antidepressant treatments. Pharmacol Biochem Behav. 1995 Aug;51(4):565-9.
• [8] The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74.
• [9] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [10] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [11] Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D3 receptor ligands. Bioorg Med Chem. 2005 Jan 3;13(1):77-87.
• [12] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [13] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3639).
• [14] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [15] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [16] Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral... Eur J Pharmacol. 2009 Mar 15;606(1-3):90-3.
• [17] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.