inderal

Propranolol (INN)
Systematic (IUPAC) name
	(RS)-1-(1-methylethylamino)-3-(1-naphthyloxy)propan-2-ol
Clinical data
Trade names	Inderal
AHFS/Drugs.com	monograph
Licence data	US FDA:link
Pregnancy; category	AU: C; US: C (Risk not ruled out); ;
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Routes of; administration	Oral, rectal, IV
Pharmacokinetic data
Bioavailability	26%
Metabolism	hepatic (extensive) 1A2, 2D6; minor: 2C19, 3A4
Biological half-life	4–5 hours
Excretion	renal <1%
Identifiers
CAS Number	525-66-6
ATC code	C07AA05
PubChem	CID: 4946
IUPHAR/BPS	564
DrugBank	DB00571
ChemSpider	4777
UNII	9Y8NXQ24VQ
KEGG	D08443
ChEBI	CHEBI:8499
ChEMBL	CHEMBL27
Chemical data
Formula	C16H21NO2
Molecular mass	259.34 g/mol
	SMILES CC(NCC(O)COC1=C(C=CC=C2)C2=CC=C1)C ;
	InChI InChI=1S/C16H21NO2/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16/h3-9,12,14,17-18H,10-11H2,1-2H3 ; Key:AQHHHDLHHXJYJD-UHFFFAOYSA-N ;
(verify)

同: Inderal
関: Propranolol

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/07 21:33:46」(JST)

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Propranolol is a sympatholytic nonselective beta blocker. It is used to treat high blood pressure, a number of heart dysrhythmias, thyrotoxicosis, and essential tremors.^[1] It is used to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks.^[1] It comes in both oral and intravenous forms.^[1]

It should not be used in those with an already slow heart rate and most of those with heart failure.^[1] Quickly stopping the medication in those with coronary artery disease may worsen symptoms.^[1] It may worsen the symptoms of asthma.^[1] Common side effects include nausea, abdominal pain, and constipation.^[1] Greater care is recommended in those with liver or kidney problems.^[1] It may possibly cause harmful effects to the infant if taken during pregnancy.^[2]

It was the first successful beta blocker developed.^[3] It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.^[4] Propranolol is available in generic form.

Medical uses

An 80 mg capsule of extended-release propranolol

A mixture of 20 mg and 10 mg propranolol tablets

Propranolol is indicated for the management of various conditions, including:

Hypertension
Angina pectoris (with the exception of variant angina)
Tachyarrhythmias
Myocardial infarction
Control of tachycardia/tremor associated with anxiety, panic, hyperthyroidism, or lithium therapy
Essential tremor
Migraine prevention^[5]^[6]
Cluster headache prevention
Hyperhidrosis
Proliferating infantile hemangioma
Some experimentation has been conducted in psychiatric areas:^[7]
- Treating the excessive drinking of fluids in psychogenic polydipsia^[8]^[9]
- Antipsychotic-induced akathisia^[10]
- Aggressive behavior of patients with brain injuries^[11]
- Post-traumatic stress disorder
- Calming down individuals with phobias by sedative effects
- Performance anxiety
- Facial blushing
Glaucoma
Thyrotoxicosis by deiodinase inhibition
Primary exertional headache^[12]

While once a first-line treatment for hypertension, the role for beta blockers was downgraded in June 2006 in the United Kingdom to fourth-line, as they do not perform as well as other drugs, particularly in the elderly, and evidence is increasing that the most frequently used beta blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes.^[13]

Propranolol is not recommended for the treatment of hypertension by the Eighth Joint National Committee (JNC 8) because a higher rate of the primary composite outcome of cardiovascular death, myocardial infarction, or stroke compared to an angiotensin receptor blocker was noted in one study.^[14]

Propranolol is also used to lower portal vein pressure in portal hypertension and prevent esophageal variceal bleeding and ascites.

Other uses

Propranolol is often used by musicians and other performers to prevent stage fright. It has been taken by surgeons to reduce their own innate hand tremors during surgery.^[15]

Propranolol is being investigated as a potential treatment for post-traumatic stress disorder(PTSD).^[16]^[17]^[18] Propranolol works to inhibit the actions of norepinephrine, a neurotransmitter that enhances memory consolidation. Individuals given propranolol immediately after trauma experienced fewer stress-related symptoms and lower rates of PTSD than respective control groups who did not receive the drug.^[19] Propranolol reduces the effects of nightmare-related cardiac activity by keeping sinus rhythm low during nightmares, as a higher pulse and increased adrenaline are associated with severe nightmares. However, results remain inconclusive as to the success of propranolol in treatment of PTSD, including nightmares experienced by those with PTSD.

Ethical and legal questions have been raised surrounding the use of propranolol-based medications for use as a "memory damper", including: altering memory-recalled evidence during an investigation, modifying behavioral response to past (albeit traumatic) experiences, the regulation of these drugs, and others.^[20] However, Hall and Carter have argued that many such objections are "based on wildly exaggerated and unrealistic scenarios that ignore the limited action of propranolol in affecting memory, underplay the debilitating impact that PTSD has on those who suffer from it, and fail to acknowledge the extent to which drugs like alcohol are already used for this purpose."^[21]

Propranolol maybe used to treat severe infantile hemangiomas (IHs) began to emerge. This treatment shows promise as being superior to corticosteroids when treating IHs. Extensive clinical case evidence and a small controlled trial support its efficacy.^[22]

Volunteers given the beta blocker propranolol scored lower on a range of psychological tests designed to reveal any racist attitudes than a group who took a placebo.^[23] The amygdala is involved in processing emotion, including fear, and has been shown to be inhibited by propranolol.^[24]

Adverse effects

Due to the high penetration across the blood-brain barrier, lipophilic beta blockers such as propranolol and metoprolol are more likely than other less lipophilic beta blockers to cause sleep disturbances such as insomnia and vivid dreams and nightmares.^[25]

Adverse drug reactions (ADRs) associated with propranolol therapy are similar to other lipophilic beta blockers.

Precautions and contraindications

Propranolol should be used with caution in people with:^[26]

Diabetes mellitus or hyperthyroidism, since signs and symptoms of hypoglycaemia may be masked
Peripheral vascular disease and Raynaud's syndrome, which may be exacerbated
Phaeochromocytoma, as hypertension may be aggravated without prior alpha blocker therapy
Myasthenia gravis, which may be worsened
Other drugs with bradycardic effects

Propranolol is contraindicated in patients with:^[26]

Reversible airways diseases, particularly asthma or chronic obstructive pulmonary disease
Bradycardia (<60 beats/minute)
Sick sinus syndrome
Atrioventricular block (second- or third-degree)
Shock
Severe hypotension
Cocaine toxicity [per American Heart Association guidelines, 2005]

Pregnancy and lactation

Propranolol, like other beta blockers, is classified as pregnancy category C in the United States and ADEC category C in Australia. Beta-blocking agents in general reduce perfusion of the placenta which may lead to adverse outcomes for the neonate, including pulmonary or cardiac complications, or premature birth. The newborn may experience additional adverse effects such as hypoglycemia and bradycardia.^[27]

Most beta-blocking agents appear in the milk of lactating women. However, propranolol is highly bound to proteins in the bloodstream and is distributed into breast milk at very low levels.^[28] These low levels are not expected to pose any risk to the breastfeeding infant, and the American Academy of Pediatrics considers propranolol therapy "generally compatible with breastfeeding".^[27]^[28]^[29]^[30]

Interactions

Since beta blockers are known to relax the cardiac muscle and to constrict the smooth muscle, these beta adrenergic antagonists, including propranolol, have an additive effect with other drugs which decrease blood pressure, or which decrease cardiac contractility or conductivity. Clinically significant interactions particularly occur with:^[26]

verapamil
epinephrine
β₂-adrenergic receptor agonists
- Salbutamol, levosalbutamol, formoterol, salmeterol, etc.
clonidine
ergot alkaloids
isoprenaline
nonsteroidal anti-inflammatory drugs
quinidine
cimetidine
lidocaine
phenobarbital
rifampicin
Fluvoxamine slows down the metabolism of propranolol significantly, leading to increased blood levels of propranolol.^[31]

Pharmacokinetics

Propranolol is rapidly and completely absorbed, with peak plasma levels achieved about 1–3 hours after ingestion. Coadministration with food appears to enhance bioavailability.^[32] Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment therefore increases its bioavailability. The main metabolite 4-hydroxypropranolol, with a longer half-life (5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active.

Propranolol is a highly lipophilic drug achieving high concentrations in the brain. The duration of action of a single oral dose is longer than the half-life and may be up to 12 hours, if the single dose is high enough (e.g., 80 mg). Effective plasma concentrations are between 10 and 100 mg/l. Toxic levels are associated with plasma concentrations above 2000 mg/l.

Mechanism of action

Propranolol is a nonselective beta blocker; that is, it blocks the action of epinephrine and norepinephrine on both β₁- and β₂-adrenergic receptors. It has little intrinsic sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdosage). Propranolol has inhibitory effects on the norepinephrine transporter and/or stimulates norepinephrine release (the concentration of norepinephrine is increased in the synapse).^[33] Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenergic activation, with the α1-adrenoceptor being particularly important for effects observed in animal models. Therefore, it can be looked upon as an indirect α1 agonist, as well as a β antagonist. Probably owing to the effect at the α1-adrenoceptor, the racemic and the individual enantiomers of propranolol have been shown to substitute for cocaine in rats, with the most potent enantiomer being S-(–)-propranolol. In addition, some evidence suggests propranolol may function as a partial agonist at one or more serotonin receptors (possibly 5-HT_1B).

Both enantiomers of the drug have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. Few studies have demonstrated propranolol's ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known "membrane stabilizing effect" and antiarrhythmic and other central nervous system effects.^[34]^[35]^[36]

History

British scientist James W. Black developed propranolol in the 1960s.^[3] In 1988, he was awarded the Nobel Prize in Medicine for this discovery. Propranolol was derived from the early β-adrenergic antagonists dichloroisoprenaline and pronethalol. The key structural modification, which was carried through to essentially all subsequent beta blockers, was the insertion of an oxymethylene group into the aryl ethanolamine structure of pronethalol, thus greatly increasing the potency of the compound. This also apparently eliminated the carcinogenicity found with pronethalol in animal models.

Newer, more cardio-selective beta blockers (such as nebivolol, carvedilol, or metoprolol) are now used in the treatment of hypertension.

Society and culture

In a 1987 study by the International Conference of Symphony and Opera Musicians, 27% of interviewed members admitted to using beta blockers such as propranolol for musical performances.^[37] For about 10-16% of performers, their degree of stage fright is considered pathological.^[37]^[38] Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.^[39] This can be seen as giving participating individuals an unfair advantage, especially in competitions, akin to the use of performance-enhancing drugs in athletes.^[40]

Brandnames

Propranolol is marketed in India under brand names such as Ciplar and Ciplar LA by Cipla, also other brands from AstraZeneca and Wyeth under brand names Inderal, Inderal LA, Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Sumial, Anaprilinum, and Bedranol SR (Sandoz). Hemangeol, a 4.28 mg/mL solution of propranolol, is indicated for the treatment of proliferating infantile hemangioma.^[41]

Research

In 2015, a trial in women with epithelial ovarian cancer showed that the intake of a nonselective β-blocker was associated with a longer survival compared to a β₁-selective β-blocker or no β-blocker.^[42] Currently, an interventional study is being conducted at the M.D. Anderson Cancer Center to access the feasibility of a nonselective β-blocker plus standard chemotherapy (paclitaxel and carboplatin or possibly docetaxel) to treat ovarian cancer.^[43]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h "Propranolol hydrochloride". Monograph. The American Society of Health-System Pharmacists. Retrieved 1 January 2015.
^ "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Retrieved 22 April 2014.
^ ^a ^b Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC (1964). "A new adrenergic betareceptor antagonist". The Lancet 283 (7342): 1080–1081. doi:10.1016/S0140-6736(64)91275-9. PMID 14132613.
^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ Shields, Kevin G.; Peter J. Goadsby (January 2005). "Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine?". Brain 128 (1): 86–97. doi:10.1093/brain/awh298. Retrieved 17 August 2012.
^ Eadie, M.; J. H. Tyrer (1985). The Biochemistry of Migraine. New York: Springer. p. 148. ISBN 9780852007310. OCLC 11726870. ^{[dead link]}
^ Kornischka J, Cordes J, Agelink MW (April 2007). "[40 years beta-adrenoceptor blockers in psychiatry]". Fortschritte Der Neurologie-Psychiatrie (in German) 75 (4): 199–210. doi:10.1055/s-2006-944295. PMID 17200914.
^ Vieweg V, Pandurangi A, Levenson J, Silverman J (1994). "The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia". International Journal of Psychiatry in Medicine 24 (4): 275–303. doi:10.2190/5WG5-VV1V-BXAD-805K. PMID 7737786.
^ Kishi Y, Kurosawa H, Endo S (1998). "Is propranolol effective in primary polydipsia?". International Journal of Psychiatry in Medicine 28 (3): 315–25. doi:10.2190/QPWL-14H7-HPGG-A29D. PMID 9844835.
^ Kramer MS, Gorkin R, DiJohnson C (1989). "Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study". The Hillside Journal of Clinical Psychiatry 11 (2): 107–19. PMID 2577308.
^ Thibaut F, Colonna L (1993). "[Anti-aggressive effect of beta-blockers]". L'Encéphale (in French) 19 (3): 263–7. PMID 7903928.
^ Clinical summary
^ Sheetal Ladva (28 June 2006). "NICE and BHS launch updated hypertension guideline". National Institute for Health and Clinical Excellence. Retrieved 11 October 2009.
^ Paul A. James, MD; et al. (5 February 2014). "2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults". The Journal of the American Medical Association. Retrieved 23 March 2015.
^ Elman MJ, Sugar J, Fiscella R, et al. (1998). "The effect of propranolol versus placebo on resident surgical performance". Transactions of the American Ophthalmological Society 96: 283–91; discussion 291–4. PMC 1298399. PMID 10360293.
^ "Doctors test a drug to ease traumatic memories - Mental Health - MSNBC.com". Retrieved 30 June 2007.
^ Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK (May 2008). "Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder". Journal of Psychiatric Research 42 (6): 503–6. doi:10.1016/j.jpsychires.2007.05.006. PMID 17588604.
^ A pill to forget
^ Vaiva, G.; Ducrocq, F.; Jezekiel, K.; Averland, B.; Lestavel, P.; Brunet, A.; Marmar, C.R. (2003). "Immediate treatment with propranolol decreases post-traumatic stress disorder two months after trauma". Biological Psychiatry 54: 947–949. doi:10.1016/s0006-3223(03)00412-8.
^ Kolber, Adam J. (2006). "Therapeutic Forgetting: The Legal and Ethical Implications of Memory Dampening". Vanderbilt Law Review, San Diego Legal Studies Paper No. 07-37. 59: 1561.
^ Hall, Wayne; Carter, Adrian (2007). "Debunking Alarmist Objections to the Pharmacological Prevention of PTSD". American Journal of Bioethics 7 (9): 23–25. doi:10.1080/15265160701551244. |access-date= requires |url= (help)
^ Hogeling, M. (2012). "Propranolol for Infantile Hemangiomas: A Review". Current Dermatology Reports: Online-first. doi:10.1007/s13671-012-0026-6.
^ Sheetal Ladva (15 March 2012). "Drug 'reduces implicit racial bias,' study suggests". Oxford Medical School. Retrieved 16 March 2012.
^ Pill for Racism
^ Cruickshank JM (2010). "Beta-blockers and heart failure". Indian Heart J 62 (2): 101–10. PMID 21180298.
^ ^a ^b ^c Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
^ ^a ^b Sweetman, Sean C., ed. (2009). "Cardiovascular Drugs". Martindale: The complete drug reference (36th ed.). London: Pharmaceutical Press. pp. 1226–1381. ISBN 978-0-85369-840-1.
^ ^a ^b [No authors listed] (2007). "Propranolol". In: Drugs and Lactation Database. U.S. National Library of Medicine Toxicology Data Network. Retrieved 25 February 2013.
^ [No authors listed] (September 2001). "Transfer of drugs and other chemicals into human milk". Pediatrics 108 (3): 776–89. PMID 11533352.
^ Spencer JP, Gonzalez LS, Barnhart DJ (July 2001). "Medications in the breast-feeding mother". Am Fam Physician 64 (1): 119–26. PMID 11456429.
^ van Harten J (1995). "Overview of the pharmacokinetics of fluvoxamine". Clinical Pharmacokinetics 29 (Suppl 1): 1–9. doi:10.2165/00003088-199500291-00003. PMID 8846617.
^ Rang, Humphrey P. (2011). Rang & Dale's pharmacology (7th ed.). Edinburgh: Churchill Livingstone. p. 106. ISBN 9780702034718.
^ Young R, Glennon RA (April 2009). "S(-)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats". Psychopharmacology (Berl.) 203 (2): 369–82. doi:10.1007/s00213-008-1317-2. PMID 18795268.
^ Wang D. W., Mistry A. M., Kahlig K. M., Kearney J. A., Xiang J., George A. L. Jr (2010). "Propranolol blocks cardiac and neuronal voltage-gated sodium channels". Front. Pharmacol 1: 144. doi:10.3389/fphar.2010.00144.
^ Bankston J. R., Kass R. S. (2010). "Molecular determinants of local anesthetic action of beta-blocking drugs: implications for therapeutic management of long QT syndrome variant 3". J. Mol. Cell. Cardiol 48: 246–253. doi:10.1016/j.yjmcc.2009.05.012.
^ Desaphy J. F., Pierno S., De Luca A., Didonna P., Camerino D. C. (2003). "Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders". Mol. Pharmacol 63 (3): 659–670. doi:10.1124/mol.63.3.659. PMID 12606775.
^ ^a ^b Fishbein M, Middlestadt SE, Ottati V, Straus S, Ellis A (1988). "Medical problems among ICSOM musicians: overview of a national survey". Med Probl Perform Artist 3: 1–8.
^ Steptoe A, Malik F, Pay C, Pearson P, Price C, Win Z (1995). "The impact of stage fright on student actors". Br J Psychol 86: 27–39. doi:10.1111/j.2044-8295.1995.tb02544.x.
^ Alan H. Lockwood (1989). "Medical Problems of Musicians". NEJM 320 (4): 221–227. doi:10.1056/nejm198901263200405.
^ Thomas H. Murray (1983). "The Coercive Power of Drugs in Sports". Hastings Center Report 13 (4): 24–30. doi:10.2307/3561718.
^ "Hemangeol - Food and Drug Administration" (PDF). 1 March 2014. Retrieved 23 March 2015.
^ A.K. Sood, J.L.Watkins, P.H. Thaker (2015). "Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer". Cancer: Online-first. doi:10.1002/cncr.29392.
^ https://clinicaltrials.gov/show/NCT01504126. Retrieved 17 October 2015. Missing or empty |title= (help)

External links

Stapleton MP (1997). "Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology". Texas Heart Institute Journal 24 (4): 336–42. PMC 325477. PMID 9456487.
Scientific American Interview with James McGaugh^{[dead link]}
U.S. National Library of Medicine: Drug Information Portal - Propranolol

UpToDate Contents

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English Journal

Protective effects of the standardized extract of Zingiber officinale on myocardium against isoproterenol-induced biochemical and histopathological alterations in rats.

Amran AZ1, Jantan I, Dianita R, Buang F.
Pharmaceutical biology.Pharm Biol.2015 Dec;53(12):1795-802. doi: 10.3109/13880209.2015.1008147. Epub 2015 Apr 14.
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PMID 25868620

Monitoring binding affinity between drug and α1-acid glycoprotein in real time by Venturi easy ambient sonic-spray ionization mass spectrometry.

Liu N1, Lu X2, Yang Y3, Yao CX3, Ning B2, He D4, He L5, Ouyang J6.
Talanta.Talanta.2015 Oct 1;143:240-4. doi: 10.1016/j.talanta.2015.04.047. Epub 2015 May 2.
A new approach for monitoring the binding affinity between drugs and alpha 1-acid glycoprotein in real time was developed based on a combination of drug-protein reaction followed by Venturi easy ambient sonic-spray ionization mass spectrometry determination of the free drug concentrations. A known b
PMID 26078155

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Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we
PMID 25963796

Japanese Journal

補助人工心臓多変数制御のための循環系応答の解析

馮金山,吉澤誠,竹田宏,三浦誠,山家智之,片平美明,仁田新一
医用電子と生体工学 28(2), 122-129, 1990
… In the case of the adult goats whose cardiac functions were supressed by Inderal (propranolol), LVADF and AOP could be controlled by changing τ. …
NAID 130004326769

Ｉｎｄｅｒａｌ　ＬＡによるβ遮断効果と血中Ｐｒｏｐｒａｎｏｌｏｌおよびその代謝物の体内動態

高橋晴美,緒方宏泰,義村尚美,柏田和子,大平峰子,荻原真理,須永達也,染谷一彦,岩下聆
臨床薬理 18(1), 277-278, 1987
NAID 130002047095

インデラルLAの品質試験

上野和行,和田恭一
病院薬学 11(4), 359-362, 1985-08-20
… The quality test of a commercial propranolol hydrochloride sustained-release preparation (Inderal LA) was conducted from 3 directions: weight variation, content uniformity and dissolution. …
NAID 110001798094

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[AHFS2015-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h "Propranolol hydrochloride". Monograph. The American Society of Health-System Pharmacists. Retrieved 1 January 2015.

[2] "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Retrieved 22 April 2014.

[Black_JW.2C_Crowther_AF.2C_Shanks_RG.2C_Smith_LH.2C_Dornhorst_AC_1964_1080.E2.80.931081-3] Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC (1964). "A new adrenergic betareceptor antagonist". The Lancet 283 (7342): 1080–1081. doi:10.1016/S0140-6736(64)91275-9. PMID 14132613.

[4] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[5] Shields, Kevin G.; Peter J. Goadsby (January 2005). "Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine?". Brain 128 (1): 86–97. doi:10.1093/brain/awh298. Retrieved 17 August 2012.

[6] Eadie, M.; J. H. Tyrer (1985). The Biochemistry of Migraine. New York: Springer. p. 148. ISBN 9780852007310. OCLC 11726870. ^{[dead link]}

[pmid17200914-7] Kornischka J, Cordes J, Agelink MW (April 2007). "[40 years beta-adrenoceptor blockers in psychiatry]". Fortschritte Der Neurologie-Psychiatrie (in German) 75 (4): 199–210. doi:10.1055/s-2006-944295. PMID 17200914.

[pmid7737786-8] Vieweg V, Pandurangi A, Levenson J, Silverman J (1994). "The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia". International Journal of Psychiatry in Medicine 24 (4): 275–303. doi:10.2190/5WG5-VV1V-BXAD-805K. PMID 7737786.

[pmid9844835-9] Kishi Y, Kurosawa H, Endo S (1998). "Is propranolol effective in primary polydipsia?". International Journal of Psychiatry in Medicine 28 (3): 315–25. doi:10.2190/QPWL-14H7-HPGG-A29D. PMID 9844835.

[pmid2577308-10] Kramer MS, Gorkin R, DiJohnson C (1989). "Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study". The Hillside Journal of Clinical Psychiatry 11 (2): 107–19. PMID 2577308.

[pmid7903928-11] Thibaut F, Colonna L (1993). "[Anti-aggressive effect of beta-blockers]". L'Encéphale (in French) 19 (3): 263–7. PMID 7903928.

[12] Clinical summary

[13] Sheetal Ladva (28 June 2006). "NICE and BHS launch updated hypertension guideline". National Institute for Health and Clinical Excellence. Retrieved 11 October 2009.

[14] Paul A. James, MD; et al. (5 February 2014). "2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults". The Journal of the American Medical Association. Retrieved 23 March 2015.

[15] Elman MJ, Sugar J, Fiscella R, et al. (1998). "The effect of propranolol versus placebo on resident surgical performance". Transactions of the American Ophthalmological Society 96: 283–91; discussion 291–4. PMC 1298399. PMID 10360293.

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