Nadolol

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Nadolol
Nadolol.svg
Systematic (IUPAC) name

* rel-(2R,3S)-5-{[(2R)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol

  • (2R*,3S*)-5-{[(2R*)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol
Clinical data
Trade namesCorgard
AHFS/Drugs.commonograph
MedlinePlusa682666
Pregnancy cat.
Legal status
RoutesOral
Pharmacokinetic data
Protein binding30%
MetabolismNil
Half-life14-24 hours
ExcretionRenal and fecal (unchanged)
Identifiers
CAS number42200-33-9 YesY
ATC codeC07AA12
PubChemCID 39147
IUPHAR ligand554
DrugBankDB01203
ChemSpider35815 YesY
UNIIFEN504330V YesY
KEGGD00432 YesY
ChEMBLCHEMBL649 YesY
Chemical data
FormulaC17H27NO4 
Mol. mass309.401 g/mol
 YesY (what is this?)  (verify)
 
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Nadolol
Nadolol.svg
Systematic (IUPAC) name

* rel-(2R,3S)-5-{[(2R)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol

  • (2R*,3S*)-5-{[(2R*)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol
Clinical data
Trade namesCorgard
AHFS/Drugs.commonograph
MedlinePlusa682666
Pregnancy cat.
Legal status
RoutesOral
Pharmacokinetic data
Protein binding30%
MetabolismNil
Half-life14-24 hours
ExcretionRenal and fecal (unchanged)
Identifiers
CAS number42200-33-9 YesY
ATC codeC07AA12
PubChemCID 39147
IUPHAR ligand554
DrugBankDB01203
ChemSpider35815 YesY
UNIIFEN504330V YesY
KEGGD00432 YesY
ChEMBLCHEMBL649 YesY
Chemical data
FormulaC17H27NO4 
Mol. mass309.401 g/mol
 YesY (what is this?)  (verify)

Nadolol (Corgard, Anabet, Solgol, Corzide, Alti-Nadolol, Apo-Nadol, Novo-Nadolol) is a non-selective beta blocker used in the treatment of high blood pressure and chest pain (its only FDA approved uses).[1] Additionally, it is often prescribed in the treatment of migraine headaches, adult attention deficit hyperactivity disorder,[2] essential tremor, and Parkinson's disease.[3][4][5]

Pharmacology[edit]

Main article: Beta-blocker

Nadolol is a non-selective beta blocker; that is, it non-selectively blocks both beta-1 and beta-2 receptors. It has a preference for beta-1 receptors, which are predominantly located in the heart, thereby inhibiting the effects of catecholamines and causing a decrease in heart rate and blood pressure. Its inhibition of beta-2 receptors, which are mainly located in the bronchial smooth muscle of the airways, leads to airway constriction similar to that seen in asthma. Inhibition of beta-1 receptors in the juxtaglomerular apparatus of the kidney inhibits the renin-angiotensin system, causing a decrease in vasoconstriction and a decrease in water retention. Nadolol's inhibition of beta-1 receptors in the heart and kidney leads to its effects on lowering blood pressure.

The drug impairs AV node conduction and decreases sinus rate.

Nadolol may also increase plasma triglycerides and decrease HDL-cholesterol levels.

Indications[edit]

Nadolol has U.S. Food and Drug Administration approved indications for:

Off-label uses[edit]

Nadolol is used in the treatment of a number of neurological disorders such as migraine, adult ADHD, essential tremor, Parkinson's disease. Prevention of migraine headaches with nadolol is well documented.[1]
A case report study from Harvard Medical School, published in 1991, described three adult patients with ADHD for whom traditional psychostimulant therapy (with methylphenidate) was either ineffective or wasn't well tolerated. Adding nadolol to the psychostimulant monotherapy resulted in improved attention and focus with decreased side effects. This suggested that combination therapy with nadolol and a psychostimulant (such as methylphenidate or dexamphetamine) might be effective for treatment-resistant ADHD in adults.[6][7]
Nadolol is also used to control tremors in degenerative diseases of the central nervous system (such as essential tremor) or as an anti-tremor agent in the treatment of Parkinson's disease.[8]
Nadolol is one of the preferred beta-blockers in the management of patients with LQTS for shortening of the QT interval and prevention of ventricular arrhythmia. It is more efficacious than metoprolol in the prevention of breakthrough cardiac events while on therapy and is equivalent to propranolol.[9] Nadolol has the advantage of once daily dosing and thus improved patient compliance.

Contraindications[edit]

Patients whose heart rate is largely mediated by the sympathetic nervous system (e.g. patients with congestive heart failure or myocardial infarct) should avoid nadolol as it inhibits sympathetic function. Nadolol is also contraindicated in patients with bradycardia (slow heart rate) because of its vasodilatory effects and tendency to cause bradycardia.

Because of its beta-2 activity, nadolol causes pulmonary bronchoconstriction and should be avoided in asthma patients in preference of a beta-1 blocker. However, evidence from a 2008 study suggests that long-term non-selective beta-blocker use may actually prove to be beneficial in mild asthma.[10]

Because nadolol, like other beta-2 blockers, inhibits the synthesis and release of glucose in response to hypoglycemia, it slows patients' recovery from acute hypoglycemic episodes and should be avoided in patients getting treatment for diabetes mellitus. In patients with insulin-dependent diabetes, a selective beta-1 blocker is preferred over non-selective blockers.

In a small study of 10 healthy individuals, green tea decreased the maximum plasma concentration and total concentration of Nadolol by over 85%. As such, it is suggested that green tea should be avoided when taking SLCO1A2 based drugs.[11]

Side effects[edit]

Chemistry[edit]

Nadolol is a mixture of stereoisomers. It is polar and hydrophilic, with low lipid solubility.

Four stereoisomers of nadolol

Synthesis[edit]

Nadolol synthesis:[12]

See also[edit]

References[edit]

  1. ^ a b c Drug Facts And Comparisons (2011 ed.). 77 Westport Plaza, Suite 450, St. Louis, Missouri: Wolters Kluwer Health. pp. (4)775. 
  2. ^ http://books.google.com/books?id=EkyTTvjNRZAC&pg=PA669&lpg=PA669&dq=Nadolol+for+ADHD&source=bl&ots=AGG0LAgDus&sig=ctayeAWE3Nkoki-_EhfeLJ2uR1I&hl=en&sa=X&ei=9a40UvX7G8nDqQHSm4HQCg&ved=0CHYQ6AEwCDgK#v=onepage&q=Nadolol%20for%20ADHD&f=true
  3. ^ http://books.google.com/books?id=EkyTTvjNRZAC&pg=PA669&lpg=PA669&dq=Nadolol+for+ADHD&source=bl&ots=AGG0LAgDus&sig=ctayeAWE3Nkoki-_EhfeLJ2uR1I&hl=en&sa=X&ei=9a40UvX7G8nDqQHSm4HQCg&ved=0CHYQ6AEwCDgK#v=onepage&q=Nadolol%20for%20ADHD&f=true
  4. ^ http://www.ncbi.nlm.nih.gov/pubmed/6348587
  5. ^ http://www.drugs.com/dosage/nadolol.html#Usual_Adult_Dose_for_Parkinsonian_Tremor
  6. ^ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1940895&dopt=Abstract
  7. ^ http://books.google.com/books?id=EkyTTvjNRZAC&pg=PA669&lpg=PA669&dq=Nadolol+for+ADHD&source=bl&ots=AGG0LAgDus&sig=ctayeAWE3Nkoki-_EhfeLJ2uR1I&hl=en&sa=X&ei=9a40UvX7G8nDqQHSm4HQCg&ved=0CHYQ6AEwCDgK#v=onepage&q=Nadolol%20for%20ADHD&f=true
  8. ^ http://www.drugs.com/dosage/nadolol.html#Usual_Adult_Dose_for_Parkinsonian_Tremor
  9. ^ Chockalingam, P; Crotti, L; Girardengo, G; Johnson, JN; Harris, KM; van der Heijden, JF; Hauer, RN; Beckmann, BM; Spazzolini, C; Rordorf, R; Rydberg, A; Clur, SA; Fischer, M; van den Heuvel, F; Kääb, S; Blom, NA; Ackerman, MJ; Schwartz, PJ; Wilde, AA (Nov 13, 2012). "Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol". Journal of the American College of Cardiology 60 (20): 2092–9. doi:10.1016/j.jacc.2012.07.046. PMID 23083782. 
  10. ^ http://ajrcmb.atsjournals.org/content/38/3/249.full
  11. ^ Misaka, S; Yatabe, J; Müller, F; Takano, K; Kawabe, K; Glaeser, H; Yatabe, M S; Onoue, S; Werba, J P; Watanabe, H; Yamada, S; Fromm, M F; Kimura, J (13 January 2014). "Green Tea Ingestion Greatly Reduces Plasma Concentrations of Nadolol in Healthy Subjects". Clinical Pharmacology & Therapeutics. doi:10.1038/clpt.2013.241. 
  12. ^ Condon, M. E.; Cimarusti, C. M.; Fox, R.; Narayanan, V. L.; Reid, J.; Sundeen, J. E.; Hauck, F. P. (1978). "Nondepressant .beta.-adrenergic blocking agents. 1. Substituted 3-amino-1-(5,6,7,8-tetrahydro-1-naphthoxy)-2-propanols". Journal of Medicinal Chemistry 21 (9): 913. doi:10.1021/jm00207a014.  edit

Notes[edit]

External links[edit]