Bitolterol

Identification

Name
Bitolterol
Accession Number
DB00901  (APRD00827)
Type
Small Molecule
Groups
Withdrawn
Description

Bitolterol mesylate is a beta-2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and COPD. Bitolterol was withdrawn from the market by Elan Pharmaceuticals in 2001. [Wikipedia]

Structure
Thumb
Synonyms
  • Bitolterol Mesylate
  • Bitolterolum
International/Other Brands
Tornalate
Categories
UNII
9KY0QXD6LI
CAS number
30392-40-6
Weight
Average: 461.5494
Monoisotopic: 461.220223107
Chemical Formula
C28H31NO5
InChI Key
FZGVEKPRDOIXJY-UHFFFAOYSA-N
InChI
InChI=1S/C28H31NO5/c1-18-6-10-20(11-7-18)26(31)33-24-15-14-22(23(30)17-29-28(3,4)5)16-25(24)34-27(32)21-12-8-19(2)9-13-21/h6-16,23,29-30H,17H2,1-5H3
IUPAC Name
4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(4-methylbenzoyloxy)phenyl 4-methylbenzoate
SMILES
CC1=CC=C(C=C1)C(=O)OC1=C(OC(=O)C2=CC=C(C)C=C2)C=C(C=C1)C(O)CNC(C)(C)C

Pharmacology

Indication

Used to dilate air passages in the lungs that have become narrowed as a result of disease or inflammation. It is used in the treatment of asthma and chronic obstructive pulmonary disease (COPD).

Structured Indications
Not Available
Pharmacodynamics

Bitolterol, an adrenergic bronchodilator, is a prodrug that widens constricted airways in the lungs by relaxing the smooth muscles that surround the bronchial passages. Bitolterol probably does not affect the inflammation in the lung, such as in bronchitis. Bitolterol is unique in that it is a prodrug because it must first be metabolized by the body before it becomes active.

Mechanism of action

Bitolterol is an adrenergic beta-2 agonist. Asthma results from a narrowing of the bronchial tubes. This narrowing is caused by muscle spasm and inflammation within the bronchial tubes. Agonism of the beta-2 adrenergic receptors by bitolterol leads to a relaxation of the smooth muscles surrounding these airway tubes which then increases the diameter and ease of air flow through the tubes.

TargetActionsOrganism
ABeta-2 adrenergic receptorNot AvailableHuman
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
DrugInteractionDrug group
AlfuzosinAlfuzosin may decrease the vasoconstricting activities of Bitolterol.Approved, Investigational
Benzylpenicilloyl PolylysineBitolterol may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BromocriptineBromocriptine may increase the hypertensive activities of Bitolterol.Approved, Investigational
BucindololBucindolol may decrease the vasoconstricting activities of Bitolterol.Investigational
BunazosinBunazosin may decrease the vasoconstricting activities of Bitolterol.Investigational
CabergolineCabergoline may increase the hypertensive activities of Bitolterol.Approved
CarvedilolCarvedilol may decrease the vasoconstricting activities of Bitolterol.Approved, Investigational
DesvenlafaxineDesvenlafaxine may increase the tachycardic activities of Bitolterol.Approved
DihydroergotamineDihydroergotamine may increase the hypertensive activities of Bitolterol.Approved
DoxazosinDoxazosin may decrease the vasoconstricting activities of Bitolterol.Approved
DuloxetineDuloxetine may increase the tachycardic activities of Bitolterol.Approved
Ergoloid mesylateErgoloid mesylate may increase the hypertensive activities of Bitolterol.Approved
ErgonovineErgonovine may increase the hypertensive activities of Bitolterol.Approved
ErgotamineErgotamine may increase the hypertensive activities of Bitolterol.Approved
IndoraminIndoramin may decrease the vasoconstricting activities of Bitolterol.Withdrawn
LabetalolLabetalol may decrease the vasoconstricting activities of Bitolterol.Approved
LevomilnacipranLevomilnacipran may increase the tachycardic activities of Bitolterol.Approved
MethylergometrineMethylergometrine may increase the hypertensive activities of Bitolterol.Approved
MilnacipranMilnacipran may increase the tachycardic activities of Bitolterol.Approved
PrazosinPrazosin may decrease the vasoconstricting activities of Bitolterol.Approved
SilodosinSilodosin may decrease the vasoconstricting activities of Bitolterol.Approved
SpironolactoneSpironolactone may decrease the vasoconstricting activities of Bitolterol.Approved
TamsulosinTamsulosin may decrease the vasoconstricting activities of Bitolterol.Approved, Investigational
TerazosinTerazosin may decrease the vasoconstricting activities of Bitolterol.Approved
TrimazosinTrimazosin may decrease the vasoconstricting activities of Bitolterol.Experimental
UrapidilUrapidil may decrease the vasoconstricting activities of Bitolterol.Investigational
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Bitolterol.Approved
VenlafaxineVenlafaxine may increase the tachycardic activities of Bitolterol.Approved
Food Interactions
Not Available

References

General References
  1. Bierman CW, Kemp JP, Nathan RA: Efficacy and safety of inhaled bitolterol mesylate via metered-dose inhaler in children with asthma. Ann Allergy Asthma Immunol. 1996 Jan;76(1):27-35. [PubMed:8564625]
  2. Friedel HA, Brogden RN: Bitolterol. A preliminary review of its pharmacological properties and therapeutic efficacy in reversible obstructive airways disease. Drugs. 1988 Jan;35(1):22-41. [PubMed:3278878]
  3. Nathan RA, Bronsky EA, Dockhorn RJ, Kemp JP: Multicenter dose-ranging study of bitolterol mesylate solution for nebulization in children with asthma. Ann Allergy. 1994 Mar;72(3):209-16. [PubMed:8129213]
  4. Messina MS: Retrospective study of bitolterol mesylate in the treatment of conditions associated with reversible bronchospasm. Adv Ther. 1995 May-Jun;12(3):157-63. [PubMed:10155050]
External Links
KEGG Drug
D00684
KEGG Compound
C06853
PubChem Compound
35330
PubChem Substance
46506895
ChemSpider
32525
ChEBI
3133
ChEMBL
CHEMBL1201295
PharmGKB
PA448644
Drugs.com
Drugs.com Drug Page
Wikipedia
Bitolterol
ATC Codes
R03AC17 — Bitolterol

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP5.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00048 mg/mLALOGPS
logP4.69ALOGPS
logP6.3ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)14ChemAxon
pKa (Strongest Basic)9.59ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area84.86 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity132.76 m3·mol-1ChemAxon
Polarizability50.91 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8753
Blood Brain Barrier-0.9679
Caco-2 permeable-0.7805
P-glycoprotein substrateSubstrate0.7533
P-glycoprotein inhibitor IInhibitor0.5438
P-glycoprotein inhibitor IINon-inhibitor0.7643
Renal organic cation transporterNon-inhibitor0.9069
CYP450 2C9 substrateNon-substrate0.7406
CYP450 2D6 substrateNon-substrate0.771
CYP450 3A4 substrateNon-substrate0.5086
CYP450 1A2 substrateNon-inhibitor0.8381
CYP450 2C9 inhibitorNon-inhibitor0.8987
CYP450 2D6 inhibitorNon-inhibitor0.8594
CYP450 2C19 inhibitorNon-inhibitor0.9
CYP450 3A4 inhibitorNon-inhibitor0.7754
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8853
Ames testNon AMES toxic0.9151
CarcinogenicityNon-carcinogens0.8648
BiodegradationNot ready biodegradable0.9876
Rat acute toxicity2.3906 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9912
hERG inhibition (predictor II)Non-inhibitor0.7982
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as depsides and depsidones. These are polycyclic compounds that is either a polyphenolic compound composed of two or more monocyclic aromatic units linked by an ester bond (depside), or a compound containing the depsidone structure (depsidone).
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Depsides and depsidones
Sub Class
Not Available
Direct Parent
Depsides and depsidones
Alternative Parents
Benzoic acid esters / Phenol esters / Phenoxy compounds / Benzoyl derivatives / Aralkylamines / Toluenes / Dicarboxylic acids and derivatives / Amino acids and derivatives / Carboxylic acid esters / 1,2-aminoalcohols
show 6 more
Substituents
Depside backbone / Benzoate ester / Phenol ester / Benzoic acid or derivatives / Phenoxy compound / Benzoyl / Aralkylamine / Toluene / Monocyclic benzene moiety / Dicarboxylic acid or derivatives
show 19 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
diester, carboxylic ester, secondary alcohol, secondary amino compound, ethanolamines (CHEBI:3133)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 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. Wilson AJ, Gibson PG, Coughlan J: Long acting beta-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev. 2000;(2):CD001281. [PubMed:10796631]
  4. Friedel HA, Brogden RN: Bitolterol. A preliminary review of its pharmacological properties and therapeutic efficacy in reversible obstructive airways disease. Drugs. 1988 Jan;35(1):22-41. [PubMed:3278878]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 14:35