Details of the Drug

General Information of Drug (ID: DMXYJOB)

• Drug Name: Phentolamine
• Synonyms: Dibasin; Fentolamin; Fentolamina; Phenotolamine; Phentalamine; Phentolaminum; Regitin; Regitine; Regitipe; Regityn; Rogitine; Phentolamine mesylate [USAN]; Phentolamine methanesulfonate; C 7337; C 7337 Ciba; Fentolamina [INN-Spanish]; Phentolamine (INN); Phentolamine [INN:BAN]; Phentolamine, methyl sulfonate; Phentolaminum [INN-Latin]; Vasomax (TN); 2-((N-(m-Hydroxyphenyl)-p-toluidino)methyl)-2-imidazoline; 2-(N'-p-Tolyl-N'-m-hydroxyphenylaminomethyl)-2-imidazoline; 2-(N-(m-Hydroxyphenyl)-p-toluidinomethyl)imidazoline; 2-(m-Hydroxy-N-p-tolylanilinomethyl)-2-imidazoline; 3-[(4,5-dihydro-1H-imidazol-2-ylmethyl)(4-methylphenyl)amino]phenol; 3-[N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-4-methylanilino]phenol

Indication

Disease Entry	ICD 11	Status	REF
Brain ischaemia	8B1Z	Approved	[1]
Dermal necrosis	MC85	Approved	[2]
Hypertensive emergency	BA03	Approved	[1]
Pheochromocytoma	5A75	Approved	[1]
Peripheral vascular disease	BD4Z	Investigative	[1]

• Therapeutic Class: Antihypertensive Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 281.35
  Logarithm of the Partition Coefficient (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• 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 42 mL/min/kg [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 19 minutes [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 15.232 micromolar/kg/day [5]
• Chemical Identifiers:
  Formula: C17H19N3O
  IUPAC Name: 3-[N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-4-methylanilino]phenol
  Canonical SMILES: CC1=CC=C(C=C1)N(CC2=NCCN2)C3=CC(=CC=C3)O
  InChI: InChI=1S/C17H19N3O/c1-13-5-7-14(8-6-13)20(12-17-18-9-10-19-17)15-3-2-4-16(21)11-15/h2-8,11,21H,9-10,12H2,1H3,(H,18,19)
  InChIKey: MRBDMNSDAVCSSF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5775
  ChEBI ID: CHEBI:8081
  CAS Number: 50-60-2
  DrugBank ID: DB00692
  TTD ID: D01JUF
  VARIDT ID: DR00754
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Protein Interaction/Cellular Processes	[7]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Protein Interaction/Cellular Processes	[7]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Protein Interaction/Cellular Processes	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[8]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Gene/Protein Processing	[8]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Gene/Protein Processing	[9]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Gene/Protein Processing	[9]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Gene/Protein Processing	[9]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Gene/Protein Processing	[10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[11]

Molecular Expression Atlas of This Drug

• The Studied Disease: Brain ischaemia
• ICD Disease Classification: 8B1Z

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

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Phentolamine and Cariprazine.	Bipolar disorder [6A60]	[12]
Olopatadine	DMKMWQG	Moderate	Additive CNS depression effects by the combination of Phentolamine and Olopatadine.	Conjunctiva disorder [9A60]	[13]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Phentolamine and Selegiline.	Depression [6A70-6A7Z]	[14]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Phentolamine and Isocarboxazid.	Depression [6A70-6A7Z]	[14]
Tranylcypromine	DMGB5RE	Moderate	Additive hypotensive effects by the combination of Phentolamine and Tranylcypromine.	Depression [6A70-6A7Z]	[14]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Phentolamine and OPC-34712.	Depression [6A70-6A7Z]	[12]
Phenelzine	DMHIDUE	Moderate	Additive hypotensive effects by the combination of Phentolamine and Phenelzine.	Depression [6A70-6A7Z]	[14]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Phentolamine and Procarbazine.	Hodgkin lymphoma [2B30]	[14]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Phentolamine and ITI-007.	Insomnia [7A00-7A0Z]	[12]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Phentolamine and Ozanimod.	Multiple sclerosis [8A40]	[14]
Promethazine	DM6I5GR	Moderate	Additive hypotensive effects by the combination of Phentolamine and Promethazine.	Nausea/vomiting [MD90]	[12]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Phentolamine and Safinamide.	Parkinsonism [8A00]	[14]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Phentolamine and Rasagiline.	Parkinsonism [8A00]	[14]
Tamsulosin	DM5QF9V	Moderate	Additive hypotensive effects by the combination of Phentolamine and Tamsulosin.	Prostate hyperplasia [GA90]	[15]
Silodosin	DMJSBT6	Moderate	Additive hypotensive effects by the combination of Phentolamine and Silodosin.	Prostate hyperplasia [GA90]	[15]
Levomepromazine	DMIKFEL	Moderate	Additive hypotensive effects by the combination of Phentolamine and Levomepromazine.	Psychotic disorder [6A20-6A25]	[12]
Mesoridazine	DM2ZGAN	Moderate	Additive hypotensive effects by the combination of Phentolamine and Mesoridazine.	Schizophrenia [6A20]	[12]
Aripiprazole	DM3NUMH	Moderate	Additive hypotensive effects by the combination of Phentolamine and Aripiprazole.	Schizophrenia [6A20]	[12]
Iloperidone	DM6AUFY	Moderate	Additive hypotensive effects by the combination of Phentolamine and Iloperidone.	Schizophrenia [6A20]	[12]
Paliperidone	DM7NPJS	Moderate	Additive hypotensive effects by the combination of Phentolamine and Paliperidone.	Schizophrenia [6A20]	[12]
Perphenazine	DMA4MRX	Moderate	Additive hypotensive effects by the combination of Phentolamine and Perphenazine.	Schizophrenia [6A20]	[12]
Molindone	DMAH70G	Moderate	Additive hypotensive effects by the combination of Phentolamine and Molindone.	Schizophrenia [6A20]	[12]
Thiothixene	DMDINC4	Moderate	Additive hypotensive effects by the combination of Phentolamine and Thiothixene.	Schizophrenia [6A20]	[12]
Trifluoperazine	DMKBYWI	Moderate	Additive hypotensive effects by the combination of Phentolamine and Trifluoperazine.	Schizophrenia [6A20]	[12]
Risperidone	DMN6DXL	Moderate	Additive hypotensive effects by the combination of Phentolamine and Risperidone.	Schizophrenia [6A20]	[12]
Amisulpride	DMSJVAM	Moderate	Additive hypotensive effects by the combination of Phentolamine and Amisulpride.	Schizophrenia [6A20]	[12]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Phentolamine and Asenapine.	Schizophrenia [6A20]	[12]
Methdilazine	DMAUHQX	Moderate	Additive hypotensive effects by the combination of Phentolamine and Methdilazine.	Vasomotor/allergic rhinitis [CA08]	[12]
Trimeprazine	DMEMV9D	Moderate	Additive hypotensive effects by the combination of Phentolamine and Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[16]

References

• [1] Phentolamine FDA Label
• [2] 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: 502).
• [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] Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol. 2009 Aug;297(2):R330-6.
• [7] Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
• [8] Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
• [9] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [10] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [11] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [12] 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]
• [13] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
• [14] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
• [15] Product Information. Flomax (tamsulosin). Boehringer-Ingelheim, Ridgefield, CT.
• [16] Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.