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Identification
Name Pindolol
Accession Number DB00960 (APRD00678)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Betapindol
  • Prinodolol
Brand names
  • Blockin L
  • Blocklin L
  • Calvisken
  • Cardilate
  • Decreten
  • Durapindol
  • Glauco-Visken
  • Pectobloc
  • Pinbetol
  • Pynastin
  • Visken
Brand name mixtures
  • Viskazide 10/25tab (Hydrochlorothiazide + Pindolol)
  • Viskazide 10/50tab (Hydrochlorothiazide + Pindolol)
Categories
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists
  • Vasodilator Agents
  • Serotonin Antagonists
CAS number 13523-86-9
Weight Average: 248.3208
Monoisotopic: 248.152477894
Chemical Formula C14H20N2O2
InChI Key InChIKey=JZQKKSLKJUAGIC-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
Plain Text
IUPAC Name
[2-hydroxy-3-(1H-indol-4-yloxy)propyl](propan-2-yl)amine
SMILES
CC(C)NCC(O)COC1=CC=CC2=C1C=CN2
Plain Text
Mass Spec show (8.8 KB)
Taxonomy
Kingdom Organic
Classes
  • Indoles and Indole Derivatives
  • Phenols and Derivatives
  • Ethers
  • Anisoles
Substructures
  • Hydroxy Compounds
  • Indoles and Indole Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Pyrroles
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Alcohols and Polyols
  • Phenyl Esters
Pharmacology
Indication For the management of hypertension, edema, ventricular tachycardias, and atrial fibrillation.
Pharmacodynamics Pindolol 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 action Pindolol 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.
Absorption Rapidly and reproducibly absorbed (bioavailability greater than 95%).
Volume of distribution
  • 2 L/kg
Protein binding 40%
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 elimination Pindolol 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 life 3 to 4 hours
Clearance
  • 50-300 mL/min [cirrhotic patients]
Toxicity LD50=263 mg/kg (orally in rats). Signs of overdose include excessive bradycardia, cardiac failure, hypotension, and bronchospasm.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00306 Pindolol Pathway SMP00306
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
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Visken 15 mg Tablet 1.52 USD tablet
Visken 10 mg Tablet 1.05 USD tablet
Pindolol 10 mg tablet 1.0 USD tablet
Pindolol 5 mg tablet 0.73 USD tablet
Apo-Pindol 15 mg Tablet 0.61 USD tablet
Gen-Pindolol 15 mg Tablet 0.61 USD tablet
Novo-Pindol 15 mg Tablet 0.61 USD tablet
Nu-Pindol 15 mg Tablet 0.61 USD tablet
Pms-Pindolol 15 mg Tablet 0.61 USD tablet
Sandoz Pindolol 15 mg Tablet 0.61 USD tablet
Visken 5 mg Tablet 0.61 USD tablet
Apo-Pindol 10 mg Tablet 0.42 USD tablet
Gen-Pindolol 10 mg Tablet 0.42 USD tablet
Novo-Pindol 10 mg Tablet 0.42 USD tablet
Nu-Pindol 10 mg Tablet 0.42 USD tablet
Pms-Pindolol 10 mg Tablet 0.42 USD tablet
Sandoz Pindolol 10 mg Tablet 0.42 USD tablet
Apo-Pindol 5 mg Tablet 0.24 USD tablet
Gen-Pindolol 5 mg Tablet 0.24 USD tablet
Novo-Pindol 5 mg Tablet 0.24 USD tablet
Nu-Pindol 5 mg Tablet 0.24 USD tablet
Pms-Pindolol 5 mg Tablet 0.24 USD tablet
Sandoz Pindolol 5 mg Tablet 0.24 USD tablet
Patents Not Available
Properties
State solid
Melting point 167-171 oC
Experimental Properties
Property Value Source
water solubility 7880 mg/L PhysProp
logP 1.9 PhysProp
Caco2 permeability -4.78 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 8.61e-01 g/l ALOGPS
logP 2.17 ALOGPS
logP 1.69 ChemAxon Molconvert
logS -2.46 ALOGPS
pKa 16.66 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 57.28 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 71.46 ChemAxon Molconvert
polarizability 28.27 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00513 Link_out
KEGG Compound C07445 Link_out
PubChem Compound 4828 Link_out
PubChem Substance 46508362 Link_out
ChemSpider 4662 Link_out
ChEBI 8214 Link_out
ChEMBL 8214 Link_out
Therapeutic Targets Database DAP000025 Link_out
PharmGKB PA450966 Link_out
Drug Product Database 828424 Link_out
RxList http://www.rxlist.com/cgi/generic3/pindolol.htm Link_out
Drugs.com http://www.drugs.com/cdi/pindolol.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/pin1611.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Pindolol Link_out
ATC Codes
  • C07AA03
  • C07AA14
  • C07AA17
AHFS Codes
  • 24:24.00
PDB Entries Not Available
FDA label Not Available
MSDS show (74.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Magnesium, potassium and zinc needs increased.
  • Take without regard to meals. Avoid alcohol.
Targets

1. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: partial agonist

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

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: partial agonist

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

Organism class: human
UniProt ID: P07550 Link_out
Gene: ADRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 1A receptor

Pharmacological action: unknown
Actions: antagonist

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

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 1B receptor

Pharmacological action: unknown
Actions: other/unknown

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

Organism class: human
UniProt ID: P28222 Link_out
Gene: HTR1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor, inducer

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

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