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Identification
NameTolazoline
Accession NumberDB00797  (APRD00170)
TypeSmall Molecule
GroupsApproved, 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
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DivascolVUAB Pharma
ImidalinAstellas Pharma
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Benzazoline hydrochloride
ThumbNot applicableDBSALT000947
Tolazoline Hydrochloride
ThumbNot applicableDBSALT000948
Categories
UNIICHH9H12AQ3
CAS number59-98-3
WeightAverage: 160.2157
Monoisotopic: 160.100048394
Chemical FormulaC10H12N2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNot Available
Direct ParentBenzene and substituted derivatives
Alternative Parents
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
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of pulmonary artery anomalies
PharmacodynamicsTolazoline is a pulmonary vasodilator indicated used to decrease pulmonary vascular resistance (PVR) in persistent pulmonary hypertension of the newborn (PPHN).
Mechanism of actionVasodilation 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point174 °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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.79 KB)
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC04AB02M02AX02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.7 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
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 differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) si...
Gene Name:
HRH2
Uniprot ID:
P25021
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
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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
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 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12