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Identification
NamePindolol
Accession NumberDB00960  (APRD00678)
TypeSmall Molecule
GroupsApproved
Description

A moderately lipophilic beta blocker (adrenergic beta-antagonists). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)

Structure
Thumb
Synonyms
SynonymLanguageCode
1-(1H-indol-4-Yloxy)-3-(isopropylamino)propan-2-olNot AvailableNot Available
1-(1H-indol-4-Yloxy)-3-(propan-2-ylamino)-propan-2-olNot AvailableNot Available
1-(1H-indol-4-Yloxy)-3-[(1-methylethyl)amino]propan-2-olNot AvailableNot Available
4-(2-Hydroxy-3-isopropylaminopropoxy)-indoleNot AvailableNot Available
BetapindolNot AvailableNot Available
Blockin LNot AvailableNot Available
Blocklin LNot AvailableNot Available
Blocklin-LNot AvailableNot Available
CalviskenNot AvailableNot Available
CardilateNot AvailableNot Available
CarviskenNot AvailableNot Available
DecretenNot AvailableNot Available
DurapindolNot AvailableNot Available
Glauco-viskenNot AvailableNot Available
PectoblocNot AvailableNot Available
PinbetolNot AvailableNot Available
PindololNot AvailableNot Available
PindololumNot AvailableNot Available
PrinodololNot AvailableNot Available
PynastinNot AvailableNot Available
ViskenNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
BetapindolNot Available
Blockin LNot Available
Blocklin LNot Available
CalviskenNot Available
DecretenNot Available
DurapindolNot Available
Glauco-ViskenNot Available
PectoblocNot Available
PinbetolNot Available
PrinodololNot Available
PynastinNot Available
ViskenNot Available
Brand mixtures
Brand NameIngredients
Viskazide 10/25tabHydrochlorothiazide + Pindolol
Viskazide 10/50tabHydrochlorothiazide + Pindolol
CategoriesNot Available
CAS number13523-86-9
WeightAverage: 248.3208
Monoisotopic: 248.152477894
Chemical FormulaC14H20N2O2
InChI KeyJZQKKSLKJUAGIC-UHFFFAOYSA-N
InChI
InChI=1S/C14H20N2O2/c1-10(2)16-8-11(17)9-18-14-5-3-4-13-12(14)6-7-15-13/h3-7,10-11,15-17H,8-9H2,1-2H3
IUPAC Name
[2-hydroxy-3-(1H-indol-4-yloxy)propyl](propan-2-yl)amine
SMILES
CC(C)NCC(O)COC1=CC=CC2=C1C=CN2
Mass Specshow(8.77 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassIndoles
Direct parentIndoles
Alternative parentsPhenol Ethers; Alkyl Aryl Ethers; Pyrroles; Secondary Alcohols; 1,2-Aminoalcohols; Polyamines; Dialkylamines
Substituentsphenol ether; alkyl aryl ether; benzene; pyrrole; 1,2-aminoalcohol; secondary alcohol; ether; secondary amine; polyamine; secondary aliphatic amine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the indoles. These are compounds containing an indole moiety, which consists of pyrrole ring fused to benzene to form 2,3-benzopyrrole.
Pharmacology
IndicationFor the management of hypertension, edema, ventricular tachycardias, and atrial fibrillation.
PharmacodynamicsPindolol is a non-selective beta-adrenergic antagonist (beta-blocker) which possesses intrinsic sympathomimetic activity (ISA) in therapeutic dosage ranges but does not possess quinidine-like membrane stabilizing activity. Pindolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Pindolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Pindolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, pindolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.
Mechanism of actionPindolol non-selectively blocks beta-1 adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. By binding beta-2 receptors in the juxtaglomerular apparatus, Pindolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.
AbsorptionRapidly and reproducibly absorbed (bioavailability greater than 95%).
Volume of distribution
  • 2 L/kg
Protein binding40%
Metabolism

Hepatic. In man, 35% to 40% is excreted unchanged in the urine and 60% to 65% is metabolized primarily to hydroxy-metabolites which are excreted as glucuronides and ethereal sulfates.

Route of eliminationPindolol undergoes extensive metabolism in animals and man. In man, 35% to 40% is excreted unchanged in the urine and 60% to 65% is metabolized primarily to hydroxy-metabolites which are excreted as glucuronides and ethereal sulfates. About 6% to 9% of an administered intravenous dose is excreted by the bile into the feces.
Half life3 to 4 hours
Clearance
  • 50-300 mL/min [cirrhotic patients]
ToxicityLD50=263 mg/kg (orally in rats). Signs of overdose include excessive bradycardia, cardiac failure, hypotension, and bronchospasm.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Pindolol Action PathwayDrug actionSMP00306
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9951
Blood Brain Barrier + 0.6929
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.6667
P-glycoprotein inhibitor I Non-inhibitor 0.9272
P-glycoprotein inhibitor II Non-inhibitor 0.9423
Renal organic cation transporter Non-inhibitor 0.8179
CYP450 2C9 substrate Non-substrate 0.8315
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Non-substrate 0.708
CYP450 1A2 substrate Non-inhibitor 0.7809
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.5
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8331
Ames test Non AMES toxic 0.9218
Carcinogenicity Non-carcinogens 0.9367
Biodegradation Not ready biodegradable 0.9843
Rat acute toxicity 2.9438 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9404
hERG inhibition (predictor II) Non-inhibitor 0.5774
Pharmacoeconomics
Manufacturers
  • Genpharm pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Nostrum laboratories inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Visken 15 mg Tablet1.52USDtablet
Visken 10 mg Tablet1.05USDtablet
Pindolol 10 mg tablet1.0USDtablet
Pindolol 5 mg tablet0.73USDtablet
Apo-Pindol 15 mg Tablet0.61USDtablet
Gen-Pindolol 15 mg Tablet0.61USDtablet
Novo-Pindol 15 mg Tablet0.61USDtablet
Nu-Pindol 15 mg Tablet0.61USDtablet
Pms-Pindolol 15 mg Tablet0.61USDtablet
Sandoz Pindolol 15 mg Tablet0.61USDtablet
Visken 5 mg Tablet0.61USDtablet
Apo-Pindol 10 mg Tablet0.42USDtablet
Gen-Pindolol 10 mg Tablet0.42USDtablet
Novo-Pindol 10 mg Tablet0.42USDtablet
Nu-Pindol 10 mg Tablet0.42USDtablet
Pms-Pindolol 10 mg Tablet0.42USDtablet
Sandoz Pindolol 10 mg Tablet0.42USDtablet
Apo-Pindol 5 mg Tablet0.24USDtablet
Gen-Pindolol 5 mg Tablet0.24USDtablet
Novo-Pindol 5 mg Tablet0.24USDtablet
Nu-Pindol 5 mg Tablet0.24USDtablet
Pms-Pindolol 5 mg Tablet0.24USDtablet
Sandoz Pindolol 5 mg Tablet0.24USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point171 °CPhysProp
water solubility7880 mg/LNot Available
logP1.75SANGSTER (1994)
Caco2 permeability-4.78ADME Research, USCD
pKa9.25SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.861ALOGPS
logP2.17ALOGPS
logP1.69ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area57.28 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity71.46 m3·mol-1ChemAxon
Polarizability28.27 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3471515
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00513
KEGG CompoundC07445
PubChem Compound4828
PubChem Substance46508362
ChemSpider4662
ChEBI8214
ChEMBLCHEMBL500
Therapeutic Targets DatabaseDAP000025
PharmGKBPA450966
IUPHAR91
Guide to Pharmacology91
Drug Product Database828424
RxListhttp://www.rxlist.com/cgi/generic3/pindolol.htm
Drugs.comhttp://www.drugs.com/cdi/pindolol.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/pin1611.shtml
WikipediaPindolol
ATC CodesC07AA03C07AA14C07AA17
AHFS Codes
  • 24:24.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(74.7 KB)
Interactions
Drug Interactions
Drug
AcetohexamideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
AminophyllineAntagonism of action and increased effect of theophylline
ChlorpromazineIncreased effect of both drugs
ChlorpropamideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
ClonidineIncreased hypertension when clonidine stopped
DihydroergotamineIschemia with risk of gangrene
DiltiazemIncreased risk of bradycardia
DisopyramideThe beta-blocker, pindolol, may increase the toxicity of disopyramide.
DyphyllineAntagonism of action and increased effect of theophylline
EpinephrineHypertension, then bradycardia
ErgonovineIschemia with risk of gangrene
ErgotamineIschemia with risk of gangrene
FenoterolAntagonism
FormoterolAntagonism
GliclazideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
GlipizideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
GlisoxepideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
GlyburideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
GlycodiazineThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
IbuprofenRisk of inhibition of renal prostaglandins
IndomethacinRisk of inhibition of renal prostaglandins
Insulin GlargineThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
IsoprenalineAntagonism
LidocaineThe beta-blocker increases the effect and toxicity of lidocaine
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
MethyldopaPossible hypertensive crisis
MethysergideIschemia with risk of gangrene
OrciprenalineAntagonism
OxtriphyllineAntagonism of action and increased effect of theophylline
PipobromanAntagonism
PirbuterolAntagonism
PiroxicamRisk of inhibition of renal prostaglandins
PrazosinRisk of hypotension at the beginning of therapy
ProcaterolAntagonism
RepaglinideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
SalbutamolAntagonism
SalmeterolAntagonism
TerazosinIncreased risk of hypotension. Initiate concomitant therapy cautiously.
TerbutalineAntagonism
TheophyllineAntagonism of action and increased effect of theophylline
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
TolazamideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
TolbutamideThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
VerapamilIncreased effect of both drugs
Food Interactions
  • Magnesium, potassium and zinc needs increased.
  • Take without regard to meals. Avoid alcohol.

Targets

1. Beta-1 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: partial agonist

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Joseph SS, Lynham JA, Molenaar P, Grace AA, Colledge WH, Kaumann AJ: Intrinsic sympathomimetic activity of (-)-pindolol mediated through a (-)-propranolol-resistant site of the beta1-adrenoceptor in human atrium and recombinant receptors. Naunyn Schmiedebergs Arch Pharmacol. 2003 Dec;368(6):496-503. Epub 2003 Nov 8. Pubmed
  3. Doggrell SA: Effects of (/-)- ()- and (-)-metoprolol, (/-)- ()- and (-)-pindolol, (/-)-mepindolol and (/-)-bopindolol on the rat left atria and portal vein. Gen Pharmacol. 1991;22(6):1169-77. Pubmed
  4. Berendsen HH, Broekkamp CL, Van Delft AM: Antagonism of 8-OH-DPAT-induced behaviour in rats. Eur J Pharmacol. 1990 Oct 2;187(1):97-103. Pubmed
  5. Watkins DJ, Lawrence AJ, Lewis SJ, Jarrott B: Loss of [125I]-pindolol binding to beta-adrenoceptors on rat nodose ganglion after chronic isoprenaline treatment. J Auton Nerv Syst. 1996 Aug 27;60(1-2):12-6. Pubmed
  6. Brodde OE, Michel MC, Wang XL, Zerkowski HR: Chronic beta-adrenoceptor antagonist treatment modulates human cardiac and vascular beta-adrenoceptor density in a subtype-selective fashion. J Hypertens Suppl. 1988 Dec;6(4):S497-500. Pubmed

2. Beta-2 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: partial agonist

Components

Name UniProt ID Details
Beta-2 adrenergic receptor P07550 Details

References:

  1. Rubenstein LA, Zauhar RJ, Lanzara RG: Molecular dynamics of a biophysical model for beta2-adrenergic and G protein-coupled receptor activation. J Mol Graph Model. 2006 Dec;25(4):396-409. Epub 2006 Mar 30. Pubmed
  2. Dejgaard A, Liggett SB, Christensen NJ, Cryer PE, Hilsted J: Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity. Scand J Clin Lab Invest. 1991 Dec;51(8):659-66. Pubmed
  3. Wheeldon NM, Newnham DM, Fraser GC, McDevitt DG, Lipworth BJ: The effect of pindolol on creatine kinase is not due to beta 2-adrenoceptor partial agonist activity. Br J Clin Pharmacol. 1991 Jun;31(6):723-4. Pubmed
  4. Doggrell SA: Effects of (/-)- ()- and (-)-metoprolol, (/-)- ()- and (-)-pindolol, (/-)-mepindolol and (/-)-bopindolol on the rat left atria and portal vein. Gen Pharmacol. 1991;22(6):1169-77. Pubmed
  5. Doggrell SA: Relaxant and beta 2-adrenoceptor blocking activities of (/- )-, ()- and (-)-pindolol on the rat isolated aorta. J Pharm Pharmacol. 1990 Jun;42(6):444-6. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. 5-hydroxytryptamine receptor 1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details

References:

  1. Smeraldi E, Benedetti F, Barbini B, Campori E, Colombo C: Sustained antidepressant effect of sleep deprivation combined with pindolol in bipolar depression. A placebo-controlled trial. Neuropsychopharmacology. 1999 Apr;20(4):380-5. Pubmed
  2. Haddjeri N, de Montigny C, Blier P: Modulation of the firing activity of rat serotonin and noradrenaline neurons by (+/-)pindolol. Biol Psychiatry. 1999 May 1;45(9):1163-9. Pubmed
  3. Gobert A, Millan MJ: Modulation of dialysate levels of dopamine, noradrenaline, and serotonin (5-HT) in the frontal cortex of freely-moving rats by (-)-pindolol alone and in association with 5-HT reuptake inhibitors: comparative roles of beta-adrenergic, 5-HT1A, and 5-HT1B receptors. Neuropsychopharmacology. 1999 Aug;21(2):268-84. Pubmed
  4. Andree B, Thorberg SO, Halldin C, Farde L: Pindolol binding to 5-HT1A receptors in the human brain confirmed with positron emission tomography. Psychopharmacology (Berl). 1999 Jun;144(3):303-5. Pubmed
  5. Fornal CA, Martin FJ, Metzler CW, Jacobs BL: Pindolol suppresses serotonergic neuronal activity and does not block the inhibition of serotonergic neurons produced by 8-hydroxy-2-(di-n-propylamino)tetralin in awake cats. J Pharmacol Exp Ther. 1999 Oct;291(1):229-38. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. 5-hydroxytryptamine receptor 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1B P28222 Details

References:

  1. Dawson LA, Nguyen HQ: The role of 5-HT and 5-HT receptors on the modulation of acute fluoxetine-induced changes in extracellular 5-HT: the mechanism of action of (+/-)pindolol. Neuropharmacology. 2000 Apr 3;39(6):1044-52. Pubmed
  2. Ariani K, Hamblin MW, Tan GL, Stratford CA, Ciaranello RD: G protein dependent alterations in [125I]iodocyanopindolol and +/- cyanopindolol binding at 5-HT1B binding sites in rat brain membranes. Neurochem Res. 1989 Sep;14(9):835-43. Pubmed
  3. Leonhardt S, Herrick-Davis K, Titeler M: Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. J Neurochem. 1989 Aug;53(2):465-71. Pubmed
  4. Herrick-Davis K, Titeler M, Leonhardt S, Struble R, Price D: Serotonin 5-HT1D receptors in human prefrontal cortex and caudate: interaction with a GTP binding protein. J Neurochem. 1988 Dec;51(6):1906-12. Pubmed
  5. Terron JA, Lopez-Munoz FJ, Hong E, Villalon CM: 2-(2-Aminoethyl)-quinoline (D-1997): a novel agonist at 5-hydroxytryptamine1-like receptors in the canine basilar artery. Arch Int Pharmacodyn Ther. 1994 Jan-Feb;327(1):56-68. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:25