Details of the Drug

General Information of Drug (ID: DMI40NL)

• Drug Name: Tolazoline
• Synonyms: Artonil; Benzalolin; Benzazoline; Benzidazol; Benzolin; Benzylimidazoline; Divascol; Imidalin; Imidaline; Kasimid;Lambril; Olitensol; Peripherine; Phenylmethylimidazoline; Prefaxil; Pridazole; Priscol; Priscoline; Tolazolin; Tolazolina; Tolazolinum; Vasimid; Vasodil; Vasodilatan; Dilatol ASI; Tolazine [veterinary]; Tolazoline Monohydrochloride; Ciba 3259; Benzolin (VAN); Benzolin (vasodilator); Tolazine [veterinary] (TN); Tolazolina [INN-Spanish]; Tolazoline (INN); Tolazoline [INN:BAN]; Tolazolinum [INN-Latin]; Benzolin (vasodilator) (VAN); 1H-Imidazole, 4,5-dihydro-2-(phenylmethyl)-(9CI); 2-(phenylmethyl)-4,5-dihydro-1H-imidazole; 2-BENZYL-4,5-IMIDAZOLINE HCl; 2-Benzyl-2-imidazoline; 2-Benzyl-4,5-dihydro-1H-imidazole; 2-Benzyl-4,5-imidazoline; 2-Benzylimidazoline; 4,5-Dihydro-2-(phenylmethyl)-1H-imidazole

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary hypertension	BB01	Approved	[1], [2], [3]

• Therapeutic Class: Vasodilator Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 160.22
  Topological Polar Surface Area (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property: MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 12.483 micromolar/kg/day [4]
• Chemical Identifiers:
  Formula: C10H12N2
  IUPAC Name: 2-benzyl-4,5-dihydro-1H-imidazole
  Canonical SMILES: C1CN=C(N1)CC2=CC=CC=C2
  InChI: InChI=1S/C10H12N2/c1-2-4-9(5-3-1)8-10-11-6-7-12-10/h1-5H,6-8H2,(H,11,12)
  InChIKey: JIVZKJJQOZQXQB-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5504
  ChEBI ID: CHEBI:28502
  CAS Number: 59-98-3
  DrugBank ID: DB00797
  TTD ID: D03RZV

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	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Pulmonary hypertension
• ICD Disease Classification: BB01

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 Tolazoline (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Tolazoline and Cariprazine.	Bipolar disorder [6A60]	[16]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Tolazoline and Selegiline.	Depression [6A70-6A7Z]	[17]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Tolazoline and Isocarboxazid.	Depression [6A70-6A7Z]	[17]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Tolazoline and OPC-34712.	Depression [6A70-6A7Z]	[16]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Tolazoline and Procarbazine.	Hodgkin lymphoma [2B30]	[17]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Tolazoline and ITI-007.	Insomnia [7A00-7A0Z]	[16]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Tolazoline and Ozanimod.	Multiple sclerosis [8A40]	[17]
Promethazine	DM6I5GR	Moderate	Additive hypotensive effects by the combination of Tolazoline and Promethazine.	Nausea/vomiting [MD90]	[16]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Tolazoline and Safinamide.	Parkinsonism [8A00]	[17]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Tolazoline and Rasagiline.	Parkinsonism [8A00]	[17]
Silodosin	DMJSBT6	Moderate	Additive hypotensive effects by the combination of Tolazoline and Silodosin.	Prostate hyperplasia [GA90]	[18]
Quetiapine	DM1N62C	Moderate	Additive hypotensive effects by the combination of Tolazoline and Quetiapine.	Schizophrenia [6A20]	[16]
Mesoridazine	DM2ZGAN	Moderate	Additive hypotensive effects by the combination of Tolazoline and Mesoridazine.	Schizophrenia [6A20]	[19]
Aripiprazole	DM3NUMH	Moderate	Additive hypotensive effects by the combination of Tolazoline and Aripiprazole.	Schizophrenia [6A20]	[16]
Iloperidone	DM6AUFY	Moderate	Additive hypotensive effects by the combination of Tolazoline and Iloperidone.	Schizophrenia [6A20]	[16]
Paliperidone	DM7NPJS	Moderate	Additive hypotensive effects by the combination of Tolazoline and Paliperidone.	Schizophrenia [6A20]	[16]
Perphenazine	DMA4MRX	Moderate	Additive hypotensive effects by the combination of Tolazoline and Perphenazine.	Schizophrenia [6A20]	[16]
Molindone	DMAH70G	Moderate	Additive hypotensive effects by the combination of Tolazoline and Molindone.	Schizophrenia [6A20]	[16]
Thiothixene	DMDINC4	Moderate	Additive hypotensive effects by the combination of Tolazoline and Thiothixene.	Schizophrenia [6A20]	[16]
Trifluoperazine	DMKBYWI	Moderate	Additive hypotensive effects by the combination of Tolazoline and Trifluoperazine.	Schizophrenia [6A20]	[16]
Amisulpride	DMSJVAM	Moderate	Additive hypotensive effects by the combination of Tolazoline and Amisulpride.	Schizophrenia [6A20]	[16]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Tolazoline and Asenapine.	Schizophrenia [6A20]	[16]

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: 7310).
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 006403.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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
• [5] Comparative effects of tolazoline and nitroprusside on human isolated radial artery. Ann Thorac Surg. 2006 Jan;81(1):125-31.
• [6] 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.
• [7] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [8] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [9] 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.
• [10] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [11] 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).
• [12] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [13] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [14] 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.
• [15] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [16] 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]
• [17] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
• [18] Product Information. Flomax (tamsulosin). Boehringer-Ingelheim, Ridgefield, CT.
• [19] Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.