Identification

Name
Tolazoline
Accession Number
DB00797  (APRD00170)
Type
Small Molecule
Groups
Approved, Vet approved
Description

A vasodilator that apparently has direct actions on blood vessels and also increases cardiac output. Tolazoline can interact to some degree with histamine, adrenergic, and cholinergic receptors, but the mechanisms of its therapeutic effects are not clear. It is used in treatment of persistent pulmonary hypertension of the newborn. [PubChem]

Structure
Thumb
Synonyms
  • 2-Benzyl-2-imidazoline
  • 2-Benzyl-4,5-imidazoline
  • 2-Benzylimidazoline
  • 4,5-Dihydro-2-(phenylmethyl)-1H-imidazole
  • Benzazolin
  • Tolazolin
  • Tolazolina
  • Tolazoline
  • Tolazolinum
Product Ingredients
IngredientUNIICASInChI Key
Tolazoline hydrochlorideE669Z6S1JG59-97-2RHTNTTODYGNRSP-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Priscoline hydrochlorideInjection, solution25 mg/1mLIntravenousNovartis1948-03-172008-08-18Us
International/Other Brands
Divascol (VUAB Pharma) / Imidalin (Astellas Pharma)
Categories
UNII
CHH9H12AQ3
CAS number
59-98-3
Weight
Average: 160.2157
Monoisotopic: 160.100048394
Chemical Formula
C10H12N2
InChI Key
JIVZKJJQOZQXQB-UHFFFAOYSA-N
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)
IUPAC Name
2-benzyl-4,5-dihydro-1H-imidazole
SMILES
C(C1=NCCN1)C1=CC=CC=C1

Pharmacology

Indication

For the treatment of pulmonary artery anomalies

Pharmacodynamics

Tolazoline is a pulmonary vasodilator indicated used to decrease pulmonary vascular resistance (PVR) in persistent pulmonary hypertension of the newborn (PPHN).

Mechanism of action

Vasodilation by means of a direct effect on peripheral vascular smooth muscle and indirect effects produced, in part, by release of endogenous histamine; tolazoline has moderate alpha-adrenergic blocking activity and has histamine agonist activity. Tolazoline usually reduces pulmonary arterial pressure and vascular resistance.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UHistamine H1 receptor
agonist
Human
UHistamine H2 receptor
agonist
Human
UAlpha-2C adrenergic receptor
binder
Human
UAlpha-2B adrenergic receptor
binder
Human
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidTolazoline may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Tolazoline.
AbediterolThe therapeutic efficacy of Abediterol can be decreased when used in combination with Tolazoline.
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Tolazoline.
AceclofenacThe therapeutic efficacy of Tolazoline can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Tolazoline can be decreased when used in combination with Acemetacin.
AcepromazineTolazoline may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Acepromazine.
Acetylsalicylic acidThe therapeutic efficacy of Tolazoline can be decreased when used in combination with Acetylsalicylic acid.
AdrafinilThe therapeutic efficacy of Adrafinil can be decreased when used in combination with Tolazoline.
AgmatineThe risk or severity of hypotension can be increased when Tolazoline is combined with Agmatine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014935
KEGG Compound
C07147
PubChem Compound
5504
PubChem Substance
46505641
ChemSpider
5303
BindingDB
55436
ChEBI
28502
ChEMBL
CHEMBL770
Therapeutic Targets Database
DAP000477
PharmGKB
PA451716
Wikipedia
Tolazoline
ATC Codes
M02AX02 — TolazolineC04AB02 — Tolazoline
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Novartis AG
Dosage forms
FormRouteStrength
Injection, solutionIntravenous25 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)174 °CPhysProp
water solubility373 mg/LNot Available
logP2.65SANGSTER (1993)
pKa10.3SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility1.36 mg/mLALOGPS
logP2.05ALOGPS
logP1.2ChemAxon
logS-2.1ALOGPS
pKa (Strongest Basic)10.25ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area24.39 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity49.07 m3·mol-1ChemAxon
Polarizability17.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9821
Blood Brain Barrier+0.9334
Caco-2 permeable-0.5062
P-glycoprotein substrateSubstrate0.6249
P-glycoprotein inhibitor INon-inhibitor0.9707
P-glycoprotein inhibitor IINon-inhibitor0.9188
Renal organic cation transporterInhibitor0.7923
CYP450 2C9 substrateNon-substrate0.8404
CYP450 2D6 substrateSubstrate0.6912
CYP450 3A4 substrateNon-substrate0.8088
CYP450 1A2 substrateNon-inhibitor0.6013
CYP450 2C9 inhibitorNon-inhibitor0.9629
CYP450 2D6 inhibitorInhibitor0.7446
CYP450 2C19 inhibitorNon-inhibitor0.9844
CYP450 3A4 inhibitorNon-inhibitor0.9738
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9644
Ames testNon AMES toxic0.8569
CarcinogenicityNon-carcinogens0.9492
BiodegradationNot ready biodegradable0.9824
Rat acute toxicity2.5351 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7268
hERG inhibition (predictor II)Non-inhibitor0.8357
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.79 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9400000000-7b6f1c4b249d1fba8927
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-0900000000-692cb3b89bff443fa65f
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-0900000000-03a59847388e2e741709
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-4900000000-54d799a1c61663a2e513
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9100000000-c36b35a2866405756d0a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-c543ee9f104cc9558d70

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Not Available
Direct Parent
Benzene and substituted derivatives
Alternative Parents
Imidolactams / Imidazolines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Carboxamidines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Imidolactam / Monocyclic benzene moiety / 2-imidazoline / Azacycle / Organoheterocyclic compound / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Carboximidamide / Carboxylic acid amidine / Amidine
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles (CHEBI:28502)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Teskin O, Uydes-Dogan BS, Enc Y, Alp FI, Kaleli D, Keser S, Iyigun T, Bilgen F, Dagsali S, Ozdemir O: Comparative effects of tolazoline and nitroprusside on human isolated radial artery. Ann Thorac Surg. 2006 Jan;81(1):125-31. [PubMed:16368348]
  4. Song W, Zhang Y, Xia L, Liu G: [Effects of some mexiletine derivatives on alpha 1-adrenoceptors]. Yao Xue Xue Bao. 1998;33(2):102-5. [PubMed:11938943]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Song W, Zhang Y, Xia L, Liu G: [Effects of some mexiletine derivatives on alpha 1-adrenoceptors]. Yao Xue Xue Bao. 1998;33(2):102-5. [PubMed:11938943]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Roll C, Hanssler L: [Interaction of tolazoline and cimetidine in persistent fetal circulation of the newborn infant]. Monatsschr Kinderheilkd. 1993 Apr;141(4):297-9. [PubMed:8487790]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Histamine receptor activity
Specific Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Ward RM: Pharmacology of tolazoline. Clin Perinatol. 1984 Oct;11(3):703-13. [PubMed:6386273]
  2. Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP: ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1100-7. doi: 10.1093/nar/gkr777. Epub 2011 Sep 23. [PubMed:21948594]
  3. Roll C, Hanssler L: [Interaction of tolazoline and cimetidine in persistent fetal circulation of the newborn infant]. Monatsschr Kinderheilkd. 1993 Apr;141(4):297-9. [PubMed:8487790]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Trendelenburg AU, Sutej I, Starke K: Presynaptic alpha 2A/D-autoreceptors in the brain cortex of Cercopithecus aethiops. Naunyn Schmiedebergs Arch Pharmacol. 1997 Mar;355(3):341-6. [PubMed:9089664]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Trendelenburg AU, Sutej I, Starke K: Presynaptic alpha 2A/D-autoreceptors in the brain cortex of Cercopithecus aethiops. Naunyn Schmiedebergs Arch Pharmacol. 1997 Mar;355(3):341-6. [PubMed:9089664]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:44