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Pindolol

July 24, 2017
Common Name

Pindolol Description

Pindolol is only found in individuals that have used or taken this drug. It is 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)Pindolol non-selectively blocks beta-1 adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resliting in a decrease in heart rate and blood pressure. By binding beta-2 receptors in the juxtaglomerliar 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. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 1-(1H-indol-4-Yloxy)-3-(isopropylamino)propan-2-olChEBI 1-(1H-indol-4-Yloxy)-3-(propan-2-ylamino)-propan-2-olChEBI 1-(1H-indol-4-Yloxy)-3-[(1-methylethyl)amino]propan-2-olChEBI 4-(2-Hydroxy-3-isopropylaminopropoxy)-indoleChEBI BetapindolChEBI Blockin LChEBI Blocklin LChEBI Blocklin-LChEBI CalviskenChEBI CardilateChEBI CarviskenChEBI DecretenChEBI DurapindolChEBI glauco-ViskenChEBI PectoblocChEBI PinbetolChEBI PindololumChEBI PrinodololChEBI PynastinChEBI ViskenChEBI Cardilic acidGenerator LB 46MeSH LB-46MeSH PrindololMeSH

Chemical Formlia

C14H20N2O2 Average Molecliar Weight

248.3208 Monoisotopic Molecliar Weight

248.152477894 IUPAC Name

1-(1H-indol-4-yloxy)-3-[(propan-2-yl)amino]propan-2-ol Traditional Name

1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol CAS Registry Number

13523-86-9 SMILES

CC(C)NCC(O)COC1=CC=CC2=C1C=CN2

InChI Identifier

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

InChI Key

JZQKKSLKJUAGIC-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as indoles. These are compounds containing an indole moiety, which consists of pyrrole ring fused to benzene to form 2,3-benzopyrrole. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Indoles and derivatives Direct Parent

Indoles Alternative Parents

  • Alkyl aryl ethers
  • Benzenoids
  • Pyrroles
  • Heteroaromatic compounds
  • Secondary alcohols
  • 1,2-aminoalcohols
  • Dialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Indole
  • Alkyl aryl ether
  • Benzenoid
  • Pyrrole
  • Heteroaromatic compound
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Azacycle
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Alcohol
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • indoles (CHEBI:8214 )
  • secondary amine (CHEBI:8214 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Serotonin Antagonists
  • Vasodilator Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point167 – 171 °CNot Available Boiling PointNot AvailableNot Available Water Solubility8.61e-01 g/LNot Available LogP1.9Not Available

    Predicted Properties

    Property Value Source Water Solubility0.86 mg/mLALOGPS 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-01b9-2900000000-e773b852c7d4839b531dView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-01c3-1900000000-97bebf43acd96bd5cf5bView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-01ba-0920000000-9c68ad2e49235b630737View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-ITFT , positivesplash10-01b9-0900000000-e0edd57b20d4dcecb440View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-0002-1690000000-c5bffa0f5938ebc6de4bView in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Pindolol PathwaySMP00306Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00960

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00960

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00960 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    4662 KEGG Compound ID

    C07445 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Pindolol NuGOwiki Link

    HMDB15095 Metagene Link

    HMDB15095 METLIN ID

    Not Available PubChem Compound

    4828 PDB ID

    Not Available ChEBI ID

    8214

    Product: Eltoprazine

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Download (PDF) General References Not Available

    Enzymes

    General function:
    Involved in monooxygenase 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 antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    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
    Gene Name:
    ADRB1
    Uniprot ID:
    P08588
    Molecular weight:
    51322.1
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    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:14608456 ]
    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:1687398 ]
    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:2148726 ]
    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:8884690 ]
    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:2907348 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    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:
    46458.3
    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:16574446 ]
    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:1666931 ]
    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:1678274 ]
    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:1687398 ]
    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:1979630 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
    Gene Name:
    HTR1B
    Uniprot ID:
    P28222
    Molecular weight:
    43567.5
    References
    1. Dawson LA, Nguyen HQ: The role of 5-HT(1A) and 5-HT(1B/1D) 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:10727715 ]
    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:2512511 ]
    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:2664084 ]
    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:3141589 ]
    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:7944828 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
    Gene Name:
    HTR1A
    Uniprot ID:
    P08908
    Molecular weight:
    46106.3
    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:10088139 ]
    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:10331108 ]
    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:10432475 ]
    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:10435400 ]
    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:10490909 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 25116175

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