Details of the Drug

General Information of Drug (ID: DMFAOKP)

• Drug Name: Fenoldopam
• Synonyms: Carlacor; Fenoldopamum; Fenodopam mesylate; Fenoldopamum [Latin]; SKF 82526; Carlacor (TN); Corlopam (TN); Fenoldopam (INN);Fenoldopam [INN:BAN]; SKF 82526-J; SKF-82526J; SK&F-82526; 6-chloro-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol; 9-chloro-5-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[1], [2]

• Therapeutic Class: Antihypertensive Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 305.75
  Topological Polar Surface Area (xlogp); 2.4
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 41.5 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 5 minutes [3]
  Metabolism: The drug is metabolized via the conjugation, without participation of cytochrome P-450 enzymes [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.12% [3]
  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 0.5 L/kg [3]
• Chemical Identifiers:
  Formula: C16H16ClNO3
  IUPAC Name: 9-chloro-5-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
  Canonical SMILES: C1CNCC(C2=CC(=C(C(=C21)Cl)O)O)C3=CC=C(C=C3)O
  InChI: InChI=1S/C16H16ClNO3/c17-15-11-5-6-18-8-13(9-1-3-10(19)4-2-9)12(11)7-14(20)16(15)21/h1-4,7,13,18-21H,5-6,8H2
  InChIKey: TVURRHSHRRELCG-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3341
  ChEBI ID: CHEBI:5002
  CAS Number: 67227-56-9
  DrugBank ID: DB00800
  TTD ID: D0R6BI

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D1 receptor (D1R)	TTZFYLI	DRD1_HUMAN	Agonist	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hypertension
• ICD Disease Classification: BA00-BA04

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D1 receptor (D1R)	DTT	DRD1	8.99E-01	-0.06	-0.3

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Fenoldopam (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Dronedarone	DMA8FS5	Major	Increased risk of ventricular arrhythmias by the combination of Fenoldopam and Dronedarone.	Angina pectoris [BA40]	[16]
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Cariprazine.	Bipolar disorder [6A60]	[17]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Selegiline.	Depression [6A70-6A7Z]	[18]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Isocarboxazid.	Depression [6A70-6A7Z]	[18]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Fenoldopam and OPC-34712.	Depression [6A70-6A7Z]	[17]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Procarbazine.	Hodgkin lymphoma [2B30]	[18]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Fenoldopam and ITI-007.	Insomnia [7A00-7A0Z]	[17]
Arsenic trioxide	DM61TA4	Major	Increased risk of ventricular arrhythmias by the combination of Fenoldopam and Arsenic trioxide.	Mature B-cell lymphoma [2A85]	[19]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Ozanimod.	Multiple sclerosis [8A40]	[18]
Promethazine	DM6I5GR	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Promethazine.	Nausea/vomiting [MD90]	[17]
Levomethadyl Acetate	DM06HG5	Major	Increased risk of ventricular arrhythmias by the combination of Fenoldopam and Levomethadyl Acetate.	Opioid use disorder [6C43]	[20]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Safinamide.	Parkinsonism [8A00]	[18]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Rasagiline.	Parkinsonism [8A00]	[18]
Levomepromazine	DMIKFEL	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Levomepromazine.	Psychotic disorder [6A20-6A25]	[17]
Quetiapine	DM1N62C	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Quetiapine.	Schizophrenia [6A20]	[17]
Mesoridazine	DM2ZGAN	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Mesoridazine.	Schizophrenia [6A20]	[17]
Aripiprazole	DM3NUMH	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Aripiprazole.	Schizophrenia [6A20]	[17]
Iloperidone	DM6AUFY	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Iloperidone.	Schizophrenia [6A20]	[17]
Paliperidone	DM7NPJS	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Paliperidone.	Schizophrenia [6A20]	[17]
Perphenazine	DMA4MRX	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Perphenazine.	Schizophrenia [6A20]	[17]
Molindone	DMAH70G	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Molindone.	Schizophrenia [6A20]	[17]
Thiothixene	DMDINC4	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Thiothixene.	Schizophrenia [6A20]	[17]
Trifluoperazine	DMKBYWI	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Trifluoperazine.	Schizophrenia [6A20]	[17]
Amisulpride	DMSJVAM	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Amisulpride.	Schizophrenia [6A20]	[17]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Asenapine.	Schizophrenia [6A20]	[17]
Pimozide	DMW83TP	Major	Increased risk of ventricular arrhythmias by the combination of Fenoldopam and Pimozide.	Schizophrenia [6A20]	[21]
Methdilazine	DMAUHQX	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Methdilazine.	Vasomotor/allergic rhinitis [CA08]	[17]
Trimeprazine	DMEMV9D	Moderate	Additive hypotensive effects by the combination of Fenoldopam and Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[22]
Amiodarone	DMUTEX3	Major	Increased risk of ventricular arrhythmias by the combination of Fenoldopam and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[23]

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: 985).
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [5] Etiology of iodinated radiocontrast nephrotoxicity and its attenuation by beraprost. Yakugaku Zasshi. 2008 Jul;128(7):1023-9.
• [6] Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 ... J Med Chem. 2004 Aug 12;47(17):4155-8.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist. Learn Mem. 2005 May-Jun;12(3):216-20.
• [9] Clinical pipeline report, company report or official report of Lundbeck.
• [10] A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome.Clin Neuropharmacol.2014 Jan-Feb;37(1):26-30.
• [11] Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data. CNS Drug Rev. 2001 Fall;7(3):305-16.
• [12] trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization o... J Med Chem. 2006 Nov 16;49(23):6848-57.
• [13] Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinso... J Pharmacol Exp Ther. 1998 Jul;286(1):228-33.
• [14] The D-1 dopamine receptor partial agonist, CY 208-243, exhibits antiparkinsonian activity in the MPTP-treated marmoset. Eur J Pharmacol. 1988 Nov 1;156(2):197-206.
• [15] Effect of zelandopam, a dopamine D1-like receptor agonist, in puromycin aminonucleoside nephrosis rats. Eur J Pharmacol. 2005 Mar 7;510(1-2):121-6.
• [16] Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
• [17] Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
• [18] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
• [19] Ohnishi K, Yoshida H, Shigeno K, et al. "Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia." Ann Intern Med 133 (2000): 881-5. [PMID: 11103058]
• [20] Cohen J "Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents." Am Heart J 122 (1991): 919-25. [PMID: 1678923]
• [21] Product Information. Orap Tablets (pimozide). Gate Pharmaceuticals, Sellersville, PA.
• [22] Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
• [23] Antonelli D, Atar S, Freedberg NA, Rosenfeld T "Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions." Isr Med Assoc J 7 (2005): 163-5. [PMID: 15792261]