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targets (2) transporters (1)
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Identification
Name Nadolol
Accession Number DB01203 (APRD00301)
Type small molecule
Groups approved
Description

A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for migraine disorders and for tremor. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Anabet
  • Corgard
  • Solgol
Brand name mixtures
  • Corzide Tab W Nadolol 40mg (Bendroflumethiazide + Nadolol)
  • Corzide Tab W Nadolol 80mg (Bendroflumethiazide + Nadolol)
Categories
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists
  • Sympatholytics
  • Anti-Arrhythmia Agents
CAS number 42200-33-9
Weight Average: 309.4006
Monoisotopic: 309.194008357
Chemical Formula C17H27NO4
InChI Key InChIKey=VWPOSFSPZNDTMJ-UCWKZMIHSA-N
InChI
InChI=1S/C17H27NO4/c1-17(2,3)18-9-12(19)10-22-16-6-4-5-11-7-14(20)15(21)8-13(11)16/h4-6,12,14-15,18-21H,7-10H2,1-3H3/t12?,14-,15+/m1/s1
Plain Text
IUPAC Name
(2R,3S)-5-[3-(tert-butylamino)-2-hydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol
SMILES
CC(C)(C)NCC(O)COC1=CC=CC2=C1C[C@H](O)[C@H](O)C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Naphthalenes
Substructures
  • Hydroxy Compounds
  • Naphthalenes
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Alcohols and Polyols
  • Aromatic compounds
  • Anisoles
  • Cyclohexenes and Derivatives
  • Phenyl Esters
Pharmacology
Indication Used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension.
Pharmacodynamics Nadolol is a nonselective beta-adrenergic receptor antagonist with a long half-life, and is structurally similar to propranolol. Clinical pharmacology studies have demonstrated beta-blocking activity by showing (1) reduction in heart rate and cardiac output at rest and on exercise, (2) reduction of systolic and diastolic blood pressure at rest and on exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia. Nadolol has no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, nadolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.
Mechanism of action Like other beta-adrenergic antagonists, nadolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, nadolol binds at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure. It also blocks beta-2 adrenergic receptors located in bronchiole smooth muscle, causing vasoconstriction. By binding beta-2 receptors in the juxtaglomerular apparatus, nadolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production. Nadolol therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.
Absorption Absorption of nadolol after oral dosing is variable, averaging about 30 percent.
Volume of distribution Not Available
Protein binding 30%
Metabolism

Not metabolized by the liver and excreted unchanged primarily by the kidneys.
Route of elimination Unlike many other beta-adrenergic blocking agents, nadolol is not metabolized by the liver and is excreted unchanged, principally by the kidneys. Nadolol is excreted predominantly in the urine.
Half life 14-24 hours
Clearance Not Available
Toxicity Oral, mouse: LD50 = 4500mg/kg. Symptoms of overdose include abdominal irritation, central nervous system depression, coma, extremely slow heartbeat, heart failure, lethargy, low blood pressure, and wheezing.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00303 Nadolol Pathway SMP00303
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Nadolol powder 94.8 USD g
Corgard 160 mg tablet 4.4 USD tablet
Corgard 80 mg tablet 4.33 USD tablet
Corgard 120 mg tablet 3.96 USD tablet
Corgard 40 mg tablet 3.11 USD tablet
Corgard 20 mg tablet 3.04 USD tablet
Nadolol 160 mg tablet 2.25 USD tablet
Nadolol 80 mg tablet 1.45 USD tablet
Apo-Nadol 160 mg Tablet 1.26 USD tablet
Nadolol 40 mg tablet 1.07 USD tablet
Naldol 80 mg tablet 1.03 USD tablet
Nadolol 20 mg tablet 0.92 USD tablet
Apo-Nadol 80 mg Tablet 0.37 USD tablet
Novo-Nadolol 80 mg Tablet 0.37 USD tablet
Apo-Nadol 40 mg Tablet 0.26 USD tablet
Novo-Nadolol 40 mg Tablet 0.26 USD tablet
Patents Not Available
Properties
State solid
Melting point 124-136 oC
Experimental Properties
Property Value Source
water solubility 8330 mg/L PhysProp
logP 1.2 PhysProp
Caco2 permeability -5.41 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 2.25e+00 g/l ALOGPS
logP 1.23 ALOGPS
logP 0.87 ChemAxon Molconvert
logS -2.14 ALOGPS
pKa 14.22 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 81.95 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 85.53 ChemAxon Molconvert
polarizability 34.63 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00432 Link_out
PubChem Compound 39147 Link_out
PubChem Substance 46505509 Link_out
ChemSpider 35815 Link_out
BindingDB 25766 Link_out
ChEBI 7444 Link_out
ChEMBL 7444 Link_out
Therapeutic Targets Database DAP000122 Link_out
PharmGKB PA450573 Link_out
Drug Product Database 818704 Link_out
RxList http://www.rxlist.com/cgi/generic3/nadolol.htm Link_out
Drugs.com http://www.drugs.com/cdi/nadolol.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cor1102.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Nadolol Link_out
ATC Codes
  • C07AA12
AHFS Codes
  • 24:24.00
PDB Entries Not Available
FDA label Not Available
MSDS show (74.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Magnesium, potassium and zinc needs increased.
  • Take without regard to meals.
Targets

1. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

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. Wheeldon NM, McDevitt DG, Lipworth BJ: The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade. Br J Clin Pharmacol. 1994 Aug;38(2):103-8. Pubmed
  3. Koshiji M, Ito H, Minatoguchi S, Watanabe H, Imai Y, Kakami M, Hirakawa S: A comparison of guanfacine, bunazosin, atenolol and nadolol on blood pressure and plasma noradrenaline responses to cold pressor testing. Clin Exp Pharmacol Physiol. 1992 Jul;19(7):481-8. Pubmed
  4. Varma DR, Shen H, Deng XF, Peri KG, Chemtob S, Mulay S: Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium. Br J Pharmacol. 1999 Jun;127(4):895-902. Pubmed
  5. Varma DR: Ligand-independent negative chronotropic responses of rat and mouse right atria to beta-adrenoceptor antagonists. Can J Physiol Pharmacol. 1999 Dec;77(12):943-9. Pubmed
  6. Wheeldon NM, McDevitt DG, Lipworth BJ: Cardiac effects of the beta 3-adrenoceptor agonist BRL35135 in man. Br J Clin Pharmacol. 1994 Apr;37(4):363-9. Pubmed

2. Beta-2 adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Wheeldon NM, McDevitt DG, Lipworth BJ: The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade. Br J Clin Pharmacol. 1994 Aug;38(2):103-8. Pubmed
  3. Ozakca I, Arioglu E, Guner S, Altan VM, Ozcelikay AT: Role of Beta-3-Adrenoceptor in Catecholamine-Induced Relaxations in Gastric Fundus from Control and Diabetic Rats. Pharmacology. 2007 Jul 6;80(4):227-238. Pubmed
  4. Liu YL, Toubro S, Astrup A, Stock MJ: Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans. Int J Obes Relat Metab Disord. 1995 Sep;19(9):678-85. Pubmed
  5. Wheeldon NM, McDevitt DG, Lipworth BJ: Evaluation of in vivo partial beta 1/beta 2-agonist activity: a dose-ranging study with carteolol. Br J Clin Pharmacol. 1992 Apr;33(4):411-6. Pubmed
  6. Varma DR, Shen H, Deng XF, Peri KG, Chemtob S, Mulay S: Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium. Br J Pharmacol. 1999 Jun;127(4):895-902. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Terao T, Hisanaga E, Sai Y, Tamai I, Tsuji A: Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J Pharm Pharmacol. 1996 Oct;48(10):1083-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:09

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.