Identification

Name
Metipranolol
Accession Number
DB01214  (APRD00668)
Type
Small Molecule
Groups
Approved
Description

A beta-adrenergic antagonist effective for both beta-1 and beta-2 receptors. It is used as an antiarrhythmic, antihypertensive, and antiglaucoma agent. [PubChem]

Structure
Thumb
Synonyms
  • (+-)-Metipranolol
  • Acetic acid 4-(2-hydroxy-3-isopropylamino-propoxy)-2,3,6-trimethyl-phenyl ester
  • Metipranolol
  • Metipranololum
Product Ingredients
IngredientUNIICASInChI Key
Metipranolol hydrochlorideFBW237ALKD36592-77-5BLWNYSZZZWQCKO-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MetipranololSolution / drops3 mg/1mLOphthalmicBauch & Lomb Incorporated1989-12-292012-07-31Us
OptiPranololSolution / drops3 mg/1mLOphthalmicBauch & Lomb Incorporated1989-12-292012-07-31Us
OptiPranololSolution / drops3 mg/1mLOphthalmicPhysicians Total Care, Inc.1989-12-292010-06-30Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MetipranololSolution / drops3 mg/1mLOphthalmicFalcon Pharmaceuticals2001-08-09Not applicableUs
International/Other Brands
Betanol / Disorat / OptiPranolol / Trimepranol
Categories
UNII
X39AL81KEB
CAS number
22664-55-7
Weight
Average: 309.4006
Monoisotopic: 309.194008357
Chemical Formula
C17H27NO4
InChI Key
BQIPXWYNLPYNHW-UHFFFAOYSA-N
InChI
InChI=1S/C17H27NO4/c1-10(2)18-8-15(20)9-21-16-7-11(3)17(22-14(6)19)13(5)12(16)4/h7,10,15,18,20H,8-9H2,1-6H3
IUPAC Name
4-{2-hydroxy-3-[(propan-2-yl)amino]propoxy}-2,3,6-trimethylphenyl acetate
SMILES
CC(C)NCC(O)COC1=C(C)C(C)=C(OC(C)=O)C(C)=C1

Pharmacology

Indication

Indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open angle glaucoma.

Associated Conditions
Pharmacodynamics

Metipranolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Metipranolol is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Metipranolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. Metipranolol reduces intraocular pressure with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce.

Mechanism of action

Although it is known that metipranolol binds the beta1 and beta2 adrenergic receptors, the mechanism of metipranolol's action is not known. It has no significant intrinsic sympathomimetic activity, and has only weak local anesthetic (membrane-stabilizing) and myocardial depressant activity. It appears that the ophthalmic beta-adrenergic blocking agents reduce aqueous humor production, as demonstrated by tonography and fluorophotometry. A slight increase in aqueous humor outflow may be an additional mechanism.

TargetActionsOrganism
ABeta-2 adrenergic receptor
antagonist
Human
ABeta-1 adrenergic receptor
antagonist
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
PathwayCategory
Metipranolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may decrease the antihypertensive activities of Metipranolol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Metipranolol.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Metipranolol.
AcebutololAcebutolol may increase the hypotensive activities of Metipranolol.
AceclofenacAceclofenac may decrease the antihypertensive activities of Metipranolol.
AcemetacinThe therapeutic efficacy of Metipranolol can be decreased when used in combination with Acemetacin.
AcepromazineAcepromazine may increase the hypotensive activities of Metipranolol.
AceprometazineAceprometazine may increase the hypotensive activities of Metipranolol.
AcetohexamideMetipranolol may increase the hypoglycemic activities of Acetohexamide.
AcetylcholineThe risk or severity of adverse effects can be increased when Metipranolol is combined with Acetylcholine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015345
KEGG Drug
D02374
KEGG Compound
C07915
PubChem Compound
31477
PubChem Substance
46505935
ChemSpider
29193
ChEBI
6897
ChEMBL
CHEMBL1291
Therapeutic Targets Database
DAP000480
PharmGKB
PA164748727
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Metipranolol
ATC Codes
C07BA68 — Metipranolol and thiazides, combinationsS01ED54 — Metipranolol, combinationsS01ED04 — Metipranolol

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alcon Laboratories
  • Bausch & Lomb Inc.
  • Dispensing Solutions
  • Doctor Gerhard Mann Chemisch Pharmazeutische Fabrik GmbH
  • Falcon Pharmaceuticals Ltd.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
Solution / dropsOphthalmic3 mg/1mL
Prices
Unit descriptionCostUnit
Optipranolol 0.3% Solution 10ml Bottle42.99USD bottle
Optipranolol 0.3% Solution 5ml Bottle25.99USD bottle
Optipranolol 0.3% eye drops5.08USD ml
Metipranolol 0.3% eye drops3.55USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)105-107 °CPhysProp
water solubility589 mg/LNot Available
logP2.66MANNHOLD,R ET AL. (1990)
Predicted Properties
PropertyValueSource
Water Solubility0.173 mg/mLALOGPS
logP2.13ALOGPS
logP2.74ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.79 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity86.63 m3·mol-1ChemAxon
Polarizability35.85 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8638
Blood Brain Barrier-0.9906
Caco-2 permeable-0.5988
P-glycoprotein substrateSubstrate0.6335
P-glycoprotein inhibitor INon-inhibitor0.7599
P-glycoprotein inhibitor IINon-inhibitor0.8296
Renal organic cation transporterNon-inhibitor0.9097
CYP450 2C9 substrateNon-substrate0.8014
CYP450 2D6 substrateSubstrate0.5086
CYP450 3A4 substrateNon-substrate0.6564
CYP450 1A2 substrateNon-inhibitor0.6333
CYP450 2C9 inhibitorNon-inhibitor0.8721
CYP450 2D6 inhibitorNon-inhibitor0.7104
CYP450 2C19 inhibitorNon-inhibitor0.9547
CYP450 3A4 inhibitorNon-inhibitor0.8282
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9528
Ames testNon AMES toxic0.9219
CarcinogenicityNon-carcinogens0.9205
BiodegradationNot ready biodegradable0.7546
Rat acute toxicity2.1686 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9794
hERG inhibition (predictor II)Non-inhibitor0.7745
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 phenol esters. These are aromatic compounds containing a benzene ring substituted by a hydroxyl group and an ester group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol esters
Sub Class
Not Available
Direct Parent
Phenol esters
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Secondary alcohols / Carboxylic acid esters / Amino acids and derivatives / 1,2-aminoalcohols / Monocarboxylic acids and derivatives / Dialkylamines / Organopnictogen compounds
show 3 more
Substituents
Phenol ester / Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / 1,2-aminoalcohol / Amino acid or derivatives / Carboxylic acid ester / Secondary alcohol / Carboxylic acid derivative
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, acetate ester, secondary amino compound, propanolamine (CHEBI:6897)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Drimal J, Knezl V, Magna D, Strizova K: External transport of beta-adrenergic binding sites in ischemic myocardium. Gen Physiol Biophys. 1987 Dec;6(6):583-91. [PubMed:2895037]
  4. Noack E: [Antiglaucomatous effectiveness of beta receptor blockers with special reference to metipranolol]. Klin Monbl Augenheilkd. 1986 Jul;189(1):1-3. [PubMed:2876128]
  5. Arai K, Wood JP, Osborne NN: Beta-adrenergic receptor agonists and antagonists counteract LPS-induced neuronal death in retinal cultures by different mechanisms. Brain Res. 2003 Sep 26;985(2):176-86. [PubMed:12967722]
  6. Bilcikova L, Bauer V, Kolena J: The action of adrenoceptor agonists and antagonists on the guinea pig and dog trachea. Gen Physiol Biophys. 1987 Feb;6(1):87-101. [PubMed:2885244]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 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. Drimal J, Knezl V, Magna D, Strizova K: External transport of beta-adrenergic binding sites in ischemic myocardium. Gen Physiol Biophys. 1987 Dec;6(6):583-91. [PubMed:2895037]
  4. Arai K, Wood JP, Osborne NN: Beta-adrenergic receptor agonists and antagonists counteract LPS-induced neuronal death in retinal cultures by different mechanisms. Brain Res. 2003 Sep 26;985(2):176-86. [PubMed:12967722]
  5. Bilcikova L, Bauer V, Kolena J: The action of adrenoceptor agonists and antagonists on the guinea pig and dog trachea. Gen Physiol Biophys. 1987 Feb;6(1):87-101. [PubMed:2885244]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Sternieri E, Coccia CP, Pinetti D, Guerzoni S, Ferrari A: Pharmacokinetics and interactions of headache medications, part II: prophylactic treatments. Expert Opin Drug Metab Toxicol. 2006 Dec;2(6):981-1007. doi: 10.1517/17425255.2.6.981 . [PubMed:17125412]
  2. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
  3. Iwaki M, Niwa T, Bandoh S, Itoh M, Hirose H, Kawase A, Komura H: Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432. doi: 10.1016/j.dmpk.2016.08.007. Epub 2016 Sep 2. [PubMed:27836712]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:29