Nadolol

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Nadolol
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.C (US)
Legal statusPOM (UK) -only (US)
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
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.C (US)
Legal statusPOM (UK) -only (US)
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]

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 the treatment of hypertension and for the long-term treatment of angina pectoris.[6]

Off-label uses(in Neurological disorders )[edit]

(Migraine,Adult ADHD, Essential tremor,& Parkinson's disease.)

Nadolol is used in the treatment of a number of Neurological disorders. The prevention of migraine headaches for which there is good documentation.[7] A case report study from Harvard Medical School, published in 1991, described three adult patients with ADHD unsuccessfully treated with traditional psychostimulant (amphetamine) therapy due to lack of effectiveness or intolerance of the psychostimulant. Nadolol was then added to the psychostimulant therapy and the combination of medications resulted in improved attention and focus with decreased medication side effects. This suggested the combination of nadolol and the psychostimulant might be effective for treatment-resistant adults with ADHD.[1][8]

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.[9]


Long QT Syndrome(LQTS)

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[10] . 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. (There may be new evidence indicating that long-term non-selective beta-blocker use may actually prove to be beneficial in mild asthma.[11])

As 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 their diabetes mellitus. In patients with insulin-dependent diabetes, a selective beta-1 blocker is preferred over non-selective blockers.

Side effects[edit]

Chemistry[edit]

Nadolol is polar and hydrophilic, with low lipid solubility.

Nadolol is a mixture of stereoisomers.

Four stereoisomers of nadolol

See also[edit]

References[edit]

  1. ^ Drug Facts And Comparisons. 2011 Edition. Wolters Kluwer Health, 77 Westport Plaza, Suite 450, St. Louis, Missouri. (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. ^ Drug Facts And Comparisons. 2011 Edition. Wolters Kluwer Health, 77 Westport Plaza, Suite 450, St. Louis, Missouri. (4)775.
  7. ^ Drug Facts And Comparisons. 2011 Edition. Wolters Kluwer Health, 77 Westport Plaza, Suite 450, St. Louis, Missouri. (4)775
  8. ^ 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
  9. ^ http://www.drugs.com/dosage/nadolol.html#Usual_Adult_Dose_for_Parkinsonian_Tremor
  10. ^ 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 (2012 Nov 13). "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. PMID 23083782. 
  11. ^ http://ajrcmb.atsjournals.org/cgi/content/full/38/3/249

^ Buice RG, Subramanian VS, Duchin KL, Uko-Nne S. (1996). "Bioequivalence of a highly variable drug: an experience with nadolol". Pharmaceutical Research 13 (7): 1109–15. doi:10.1023/A:1016031313065. PMID 8842054.  ^N. Hanania, S. Singh, R. El-Wali, et al. The safety and effects of the beta-blocker, nadolol, in mild asthma: An open-label pilot study Pulmonary Pharmacology & Therapeutics, Volume 21, Issue 1, Pages 134-141

External links[edit]