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Identification
NameMetipranolol
Accession NumberDB01214  (APRD00668)
TypeSmall Molecule
GroupsApproved
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
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Metipranololsolution/ drops3 mg/mLophthalmicFalcon Pharmaceuticals, Ltd.2001-08-09Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BetanolNot Available
DisoratNot Available
OptiPranololNot Available
TrimepranolNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Metipranolol hydrochloride
Thumb
  • InChI Key: BLWNYSZZZWQCKO-UHFFFAOYNA-N
  • Monoisotopic Mass: 345.170686096
  • Average Mass: 345.862
DBSALT000806
Categories
UNIIX39AL81KEB
CAS number22664-55-7
WeightAverage: 309.4006
Monoisotopic: 309.194008357
Chemical FormulaC17H27NO4
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenol esters
Direct ParentPhenol esters
Alternative Parents
Substituents
  • Phenol ester
  • Phenol ether
  • Alkyl aryl ether
  • Acetate salt
  • Secondary alcohol
  • Carboxylic acid ester
  • 1,2-aminoalcohol
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationIndicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open angle glaucoma.
PharmacodynamicsMetipranolol 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 actionAlthough 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.
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
Pathways
PathwayCategorySMPDB ID
Metipranolol Action PathwayDrug actionSMP00667
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solution/ dropsophthalmic3 mg/mL
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point105-107 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC07BA68S01ED04S01ED54
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetylcholineThe risk or severity of adverse effects can be increased when Metipranolol is combined with Acetylcholine.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Metipranolol.
BretyliumBretylium may increase the bradycardic activities of Metipranolol.
BupivacaineThe serum concentration of Bupivacaine can be increased when it is combined with Metipranolol.
ButabarbitalButabarbital may increase the hypotensive activities of Metipranolol.
ButethalButethal may increase the hypotensive activities of Metipranolol.
CabergolineMetipranolol may increase the vasoconstricting activities of Cabergoline.
CarbacholThe risk or severity of adverse effects can be increased when Metipranolol is combined with Carbachol.
CeritinibMetipranolol may increase the bradycardic activities of Ceritinib.
DronedaroneDronedarone may increase the bradycardic activities of Metipranolol.
DuloxetineMetipranolol may increase the orthostatic hypotensive activities of Duloxetine.
EsmololEsmolol may increase the bradycardic activities of Metipranolol.
FingolimodMetipranolol may increase the bradycardic activities of Fingolimod.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Metipranolol.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Metipranolol.
HexobarbitalHexobarbital may increase the hypotensive activities of Metipranolol.
IvabradineMetipranolol may increase the bradycardic activities of Ivabradine.
LacosamideMetipranolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LevodopaMetipranolol may increase the orthostatic hypotensive activities of Levodopa.
LidocaineThe serum concentration of Lidocaine can be increased when it is combined with Metipranolol.
MepivacaineThe serum concentration of Mepivacaine can be increased when it is combined with Metipranolol.
MethacholineThe risk or severity of adverse effects can be increased when Metipranolol is combined with Methacholine.
MethohexitalMethohexital may increase the hypotensive activities of Metipranolol.
MidodrineMetipranolol may increase the bradycardic activities of Midodrine.
NicorandilNicorandil may increase the hypotensive activities of Metipranolol.
NifedipineNifedipine may increase the hypotensive activities of Metipranolol.
OctreotideOctreotide may increase the bradycardic activities of Metipranolol.
OrciprenalineMetipranolol may decrease the activities of Orciprenaline.
PentobarbitalPentobarbital may increase the hypotensive activities of Metipranolol.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Metipranolol.
PrimidonePrimidone may increase the hypotensive activities of Metipranolol.
RegorafenibRegorafenib may increase the bradycardic activities of Metipranolol.
ReserpineReserpine may increase the hypotensive activities of Metipranolol.
RisperidoneMetipranolol may increase the hypotensive activities of Risperidone.
RivastigmineRivastigmine may increase the bradycardic activities of Metipranolol.
RuxolitinibRuxolitinib may increase the bradycardic activities of Metipranolol.
SecobarbitalSecobarbital may increase the hypotensive activities of Metipranolol.
SufentanilSufentanil may increase the bradycardic activities of Metipranolol.
TheophyllineMetipranolol may decrease the activities of Theophylline.
TofacitinibTofacitinib may increase the bradycardic activities of Metipranolol.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Metipranolol.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Metipranolol.
Food InteractionsNot Available

Targets

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 equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
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 ]
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 30-fold greater affinity than it does norepinephrine.
Gene Name:
ADRB2
Uniprot ID:
P07550
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 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13