Propranolol

Image:Propranolol 80mg.png propranolol]]

Image:Propranolol tablets.png

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Propranolol is used for treating various conditions, including:

• Hypertension
• Angina pectoris (with the exception of variant angina)
• Myocardial infarction
• Tachycardia (and other sympathetic nervous system symptoms, such as muscle tremor) associated with various conditions, including anxiety, panic, hyperthyroidism, and lithium therapy
• Portal hypertension, to lower portal vein pressure
• Prevention of esophageal variceal bleeding and ascites
• Anxiety
• Hypertrophic cardiomyopathy

While once a first-line treatment for hypertension, the role of 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.{{cite web | vauthors = Ladva S | title=NICE and BHS launch updated hypertension guideline | url=http://www.nice.org.uk/download.aspx?o=335988 | date=28 June 2006 | publisher=National Institute for Health and Clinical Excellence | access-date=11 October 2009 | archive-url=https://web.archive.org/web/20060924003311/http://www.nice.org.uk/download.aspx?o=335988 | archive-date=24 September 2006 | df=dmy-all }}

Propranolol is not recommended for the treatment of high blood pressure 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.{{cite journal | vauthors = James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC, Svetkey LP, Taler SJ, Townsend RR, Wright JT, Narva AS, Ortiz E | title = 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) | journal = JAMA | volume = 311 | issue = 5 | pages = 507–520 | date = February 2014 | pmid = 24352797 | doi = 10.1001/jama.2013.284427 | df = dmy-all | doi-access = free }}

Propranolol is occasionally used to treat performance anxiety, although evidence to support its use in any anxiety disorders is poor.{{cite journal | vauthors = Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A | title = Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis | journal = Journal of Psychopharmacology | volume = 30 | issue = 2 | pages = 128–139 | date = February 2016 | pmid = 26487439 | pmc = 4724794 | doi = 10.1177/0269881115612236 }} Its efficacy in managing panic disorder appears similar to benzodiazepines, while carrying lower risks for addiction or abuse. Although beta-blockers such as propranolol have been suggested to be beneficial in managing physical symptoms of anxiety, its efficacy in treating generalized anxiety disorder and panic disorder remain unestablished.{{cite journal | title = Beta-blockers in anxiety disorders | vauthors = Peggy H, Charles S | doi = 10.1016/0165-0327(87)90017-6 | url = https://www.sciencedirect.com/science/article/abs/pii/0165032787900176 | journal = Journal of Affective Disorders | volume = 13 | issue = 2 | date = October 1987 | pages = 119–130| pmid = 2890677 | url-access = subscription }} Some experimentation has been conducted in other psychiatric areas:{{cite journal | vauthors = Kornischka J, Cordes J, Agelink MW | title = 40 years beta-adrenoceptor blockers in psychiatry | language = de | journal = Fortschritte der Neurologie-Psychiatrie | volume = 75 | issue = 4 | pages = 199–210 | date = April 2007 | pmid = 17200914 | doi = 10.1055/s-2006-944295 | s2cid = 260156607 | url = https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-2006-944295| url-access = subscription }}

• Post-traumatic stress disorder (PTSD) and specific phobias
• Aggressive behavior of patients with brain injuries{{cite journal | vauthors = Thibaut F, Colonna L | title = [Anti-aggressive effect of beta-blockers] | language = fr | journal = L'Encephale | volume = 19 | issue = 3 | pages = 263–267 | year = 1993 | pmid = 7903928 }}
• Treating the excessive drinking of fluids in psychogenic polydipsia{{cite journal | vauthors = Vieweg V, Pandurangi A, Levenson J, Silverman J | title = The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia | journal = International Journal of Psychiatry in Medicine | volume = 24 | issue = 4 | pages = 275–303 | year = 1994 | pmid = 7737786 | doi = 10.2190/5WG5-VV1V-BXAD-805K | s2cid = 22703210 }}{{cite journal | vauthors = Kishi Y, Kurosawa H, Endo S | title = Is propranolol effective in primary polydipsia? | journal = International Journal of Psychiatry in Medicine | volume = 28 | issue = 3 | pages = 315–325 | year = 1998 | pmid = 9844835 | doi = 10.2190/QPWL-14H7-HPGG-A29D | s2cid = 25222454 }}

Propranolol is being investigated as a potential treatment for PTSD.{{cite web |url=http://www.nbcnews.com/id/10806799 |archive-url=https://web.archive.org/web/20131112233001/http://www.nbcnews.com/id/10806799/ |url-status=dead |archive-date=12 November 2013 |title=Doctors test a drug to ease traumatic memories - Mental Health - NBC News |website=NBC News |access-date=30 June 2007 }}{{cite journal | vauthors = Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK | title = Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder | journal = Journal of Psychiatric Research | volume = 42 | issue = 6 | pages = 503–506 | date = May 2008 | pmid = 17588604 | doi = 10.1016/j.jpsychires.2007.05.006 }}{{Cite book | vauthors = Young C, Butcher R |url=http://www.ncbi.nlm.nih.gov/books/NBK562942/ |title=Propranolol for Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness |date=2020 |publisher=Canadian Agency for Drugs and Technologies in Health |series=CADTH Rapid Response Reports |location=Ottawa (ON) |pmid=33074615}} Propranolol works to inhibit the actions of norepinephrine (noradrenaline), a neurotransmitter that enhances memory consolidation.{{Cite web |title=DocFilm – DW |url=https://www.dw.com/en/docfilm/program-294010 |access-date=2 August 2023 |website=dw.com |language=en}} In one small study, 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.{{cite journal | vauthors = Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR | title = Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma | journal = Biological Psychiatry | volume = 54 | issue = 9 | pages = 947–949 | date = November 2003 | pmid = 14573324 | doi = 10.1016/s0006-3223(03)00412-8 | s2cid = 3064619 }} Due to the fact that memories and their emotional content are reconsolidated in the hours after they are recalled/re-experienced, propranolol can also diminish the emotional impact of already formed memories; for this reason, it is also being studied in the treatment of specific phobias, such as arachnophobia, dental fear, and social phobia. It has also been found to be helpful for some individuals with misophonia.{{cite journal | vauthors = Webb J | title = β-Blockers for the Treatment of Misophonia and Misokinesia | journal = Clinical Neuropharmacology | volume = 45 | issue = 1 | pages = 13–14 | date = Jan–Feb 2022 | pmid = 35029865 | doi = 10.1097/WNF.0000000000000492 | s2cid = 245932937 }}

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 the behavioral response to past (albeit traumatic) experiences, the regulation of these drugs, and others.{{cite journal| vauthors = Kolber AJ | title=Therapeutic Forgetting: The Legal and Ethical Implications of Memory Dampening |journal=Vanderbilt Law Review, San Diego Legal Studies Paper No. 07-37. |volume=59 |page=1561 |year=2006}} 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".{{cite journal | vauthors = Hall W, Carter A | title = Debunking alarmist objections to the pharmacological prevention of PTSD | journal = The American Journal of Bioethics | volume = 7 | issue = 9 | pages = 23–25 | date = September 2007 | pmid = 17849333 | doi = 10.1080/15265160701551244 | s2cid = 27063524 }}

• Essential tremor. Evidence for use for akathisia however is insufficient{{cite journal | vauthors = Lima AR, Bacalcthuk J, Barnes TR, Soares-Weiser K | title = Central action beta-blockers versus placebo for neuroleptic-induced acute akathisia | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD001946 | date = October 2004 | volume = 2004 | pmid = 15495022 | pmc = 6599862 | doi = 10.1002/14651858.CD001946.pub2 }}
• Migraine and cluster headache prevention{{cite journal | vauthors = Shields KG, Goadsby PJ | title = Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine? | journal = Brain | volume = 128 | issue = Pt 1 | pages = 86–97 | date = January 2005 | pmid = 15574468 | doi = 10.1093/brain/awh298 | doi-access = free }}{{cite book |title=The Biochemistry of Migraine | vauthors = Eadie M, Tyrer JH |year=1985 |publisher=Springer |location=New York |isbn=9780852007310 |page=148 |oclc=11726870 |url= https://books.google.com/books?id=JYeyCc9M6acC&q=Propranolol+migraine+mechanism%2C&pg=PA148 |url-status=live |archive-url=https://web.archive.org/web/20170324030406/https://books.google.com/books?id=JYeyCc9M6acC&pg=PA148&lpg=PA148&dq=Propranolol+migraine+mechanism,&source=bl&ots=Ep2oSjxpAo&sig=7H_KHF3xoIP0nBKJJaqsDl_IhAs&hl=en&ei=TXVPTuu6DKHE4gT6gLnXBw&sa=X&oi=book_result&ct=result&resnum=4&ved=0CCoQ6AEwAzgK#v=onepage&q=Propranolol%20migraine%20mechanism%2C&f=false |archive-date=24 March 2017 }} and in primary exertional headache{{cite web | vauthors = Chan C, Goadsby PJ | veditors = Silberstein SD | date = 26 September 1996 | title = Primary exercise headache | work = MedLink | url = https://www.medlink.com/articles/primary-exercise-headache }}
• Hyperhidrosis (excessive sweating){{cn|date=June 2023}}
• Infantile hemangioma{{cite journal | vauthors = Chen T, Gudipudi R, Nguyen SA, Carroll W, Clemmens C | title = Should Propranolol Remain the Gold Standard for Treatment of Infantile Hemangioma? A Systematic Review and Meta-Analysis of Propranolol Versus Atenolol | journal = The Annals of Otology, Rhinology, and Laryngology | pages = 332–340 | date = April 2022 | volume = 132 | issue = 3 | pmid = 35466712 | doi = 10.1177/00034894221089758 | s2cid = 248375711 }}
• Glaucoma{{cn|date=June 2023}}
• Thyrotoxicosis by deiodinase inhibition{{cn|date=June 2023}}

Propranolol may be used to treat severe infantile hemangiomas (IHs). This treatment shows promise as being superior to corticosteroids when treating IHs. Extensive clinical case evidence and a small controlled trial support its efficacy.{{cite journal |journal= Current Dermatology Reports |year= 2012 |doi= 10.1007/s13671-012-0026-6 |title= Propranolol for Infantile Hemangiomas: A Review | vauthors = Hogeling M |page= Online-first |volume=1|issue= 4 |doi-access= free }}

{{See also|Beta blocker#Contraindications}}

Propranolol may be contraindicated in people with:

• Reversible airway diseases, particularly asthma or chronic obstructive pulmonary disease (COPD)
• Slow heart rate (bradycardia) (<60 beats/minute)
• Sick sinus syndrome
• Atrioventricular block (second- or third-degree)
• Shock
• Severe low blood pressure

{{See also|Beta blocker#Adverse effects}}

Propranolol should be used with caution in people with:{{cite book | veditors = Rossi S | title = Australian Medicines Handbook | date = 2006 | location = Adelaide | publisher = Australian Medicines Handbook }}

• Diabetes mellitus or hyperthyroidism, since signs and symptoms of hypoglycemia may be masked
• Peripheral artery disease and Raynaud 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, like other beta-blockers, is classified as pregnancy category C in the United States and ADEC category C in Australia. β-blocking agents in general reduce perfusion of the placenta, which may lead to adverse outcomes for the neonate, including lung or heart complications, or premature birth. The newborn may experience additional adverse effects such as low blood sugar and a slower than normal heart rate.{{Cite book| veditors = Sweetman SC |chapter=Cardiovascular Drugs|title=Martindale: The complete drug reference |edition=36th |year=2009|pages=1226–1381|publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|title-link=Martindale: The complete drug reference}}

Most β-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.[No authors listed] (2007). "Propranolol". In: Drugs and Lactation Database. U.S. National Library of Medicine Toxicology Data Network. Retrieved 25 February 2013. 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."{{cite journal |author=Committee on Drugs | title = Transfer of drugs and other chemicals into human milk | journal = Pediatrics | volume = 108 | issue = 3 | pages = 776–789 | date = September 2001 | pmid = 11533352 | doi = 10.1542/peds.108.3.776| s2cid = 27763768 | doi-access = free }}{{cite journal | vauthors = Spencer JP, Gonzalez LS, Barnhart DJ | title = Medications in the breast-feeding mother | journal = American Family Physician | volume = 64 | issue = 1 | pages = 119–126 | date = July 2001 | pmid = 11456429 }}

In overdose, propranolol is associated with seizures.{{cite journal | vauthors = Reith DM, Dawson AH, Epid D, Whyte IM, Buckley NA, Sayer GP | title = Relative toxicity of beta blockers in overdose | journal = Journal of Toxicology. Clinical Toxicology | volume = 34 | issue = 3 | pages = 273–278 | date = 1996 | pmid = 8667464 | doi = 10.3109/15563659609013789 }} Cardiac arrest may occur in propranolol overdose due to sudden ventricular arrhythmias, or cardiogenic shock which may ultimately culminate in bradycardic PEA.{{cite journal | vauthors = Holstege CP, Eldridge DL, Rowden AK | title = ECG manifestations: the poisoned patient | journal = Emergency Medicine Clinics of North America | volume = 24 | issue = 1 | pages = 159–77, vii | date = February 2006 | pmid = 16308118 | doi = 10.1016/j.emc.2005.08.012 }}

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

• Verapamil
• Epinephrine (adrenaline)
• β₂-adrenergic receptor agonists
• Salbutamol (albuterol), levosalbutamol, formoterol, salmeterol, clenbuterol, others
• Clonidine
• Ergot alkaloids
• Isoprenaline (isoproterenol)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Quinidine
• Cimetidine
• Lidocaine
• Phenobarbital
• Rifampicin
• Fluvoxamine (slows down the metabolism of propranolol significantly, leading to increased blood levels of propranolol){{cite journal | vauthors = van Harten J | title = Overview of the pharmacokinetics of fluvoxamine | journal = Clinical Pharmacokinetics | volume = 29 | issue = Suppl 1 | pages = 1–9 | year = 1995 | pmid = 8846617 | doi = 10.2165/00003088-199500291-00003 | s2cid = 71812133 }}

Propranolol is classified as a competitive non-cardioselective sympatholytic beta blocker that crosses the blood–brain barrier. It is lipid soluble and also has sodium channel-blocking effects. Propranolol is a non-selective β-adrenergic receptor antagonist, or beta blocker;{{cite book | vauthors = Al-Majed AA, Bakheit AH, Abdel Aziz HA, Alajmi FM, AlRabiah H | title = Propranolol | journal = Profiles of Drug Substances, Excipients, and Related Methodology | series = Profiles of Drug Substances, Excipients and Related Methodology | volume = 42 | pages = 287–338 | date = 2017 | pmid = 28431779 | doi = 10.1016/bs.podrm.2017.02.006 | isbn = 9780128122266 }} that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at 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. overdose).{{cite book| vauthors = Naish J, Court DS |title=Medical sciences|date=2014|isbn=978-0702052491|page=150|publisher=Elsevier Health Sciences |edition=Second}} Propranolol can cross the blood-brain barrier and exert effects in the central nervous system in addition to its peripheral activity.

In addition to blockade of adrenergic receptors, propranolol has very weak inhibitory effects on the norepinephrine transporter and/or weakly stimulates norepinephrine release (i.e., the concentration of norepinephrine is increased in the synapse).{{cite journal | vauthors = Young R, Glennon RA | title = S(-)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats | journal = Psychopharmacology | volume = 203 | issue = 2 | pages = 369–382 | date = April 2009 | pmid = 18795268 | doi = 10.1007/s00213-008-1317-2 | doi-access = free }} Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenoceptor activation, with the α₁-adrenoceptor being particularly important for effects observed in animal models. Therefore, it can be looked upon as a weak indirect α₁-adrenoceptor agonist in addition to potent β-adrenoceptor antagonist. In addition to its effects on the adrenergic system, there is evidence that indicates that propranolol may act as a weak antagonist of certain serotonin receptors, namely the 5-HT_1A, 5-HT_1B, and 5-HT_2B receptors.{{cite journal | vauthors = Davids E, Lesch KP | title = [The 5-HT1A receptor: a new effective principle in psychopharmacologic therapy?] | language = de | journal = Fortschritte der Neurologie-Psychiatrie | volume = 64 | issue = 11 | pages = 460–472 | date = November 1996 | pmid = 9064274 | doi = 10.1055/s-2007-996592 | s2cid = 147793142 }}{{cite journal | vauthors = Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP | title = International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin) | journal = Pharmacological Reviews | volume = 46 | issue = 2 | pages = 157–203 | date = June 1994 | doi = 10.1016/S0031-6997(25)06783-3 | pmid = 7938165 }} The latter may be involved in the effectiveness of propranolol in the treatment of migraine at high doses.

Both enantiomers of propranolol have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. 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.{{cite journal | vauthors = Wang DW, Mistry AM, Kahlig KM, Kearney JA, Xiang J, George AL | title = Propranolol blocks cardiac and neuronal voltage-gated sodium channels | journal = Frontiers in Pharmacology | volume = 1 | pages = 144 | year = 2010 | pmid = 21833183 | pmc = 3153018 | doi = 10.3389/fphar.2010.00144 | doi-access = free }}{{cite journal | vauthors = Bankston JR, Kass RS | title = Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3 | journal = Journal of Molecular and Cellular Cardiology | volume = 48 | issue = 1 | pages = 246–253 | date = January 2010 | pmid = 19481549 | pmc = 2813422 | doi = 10.1016/j.yjmcc.2009.05.012 }}{{cite journal | vauthors = Desaphy JF, Pierno S, De Luca A, Didonna P, Camerino DC | title = Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders | journal = Molecular Pharmacology | volume = 63 | issue = 3 | pages = 659–670 | date = March 2003 | pmid = 12606775 | doi = 10.1124/mol.63.3.659 | url = http://pdfs.semanticscholar.org/20af/2edd8d1cb9f3874aee83a478c5af152298c0.pdf | s2cid = 631197 | archive-url = https://web.archive.org/web/20190220073326/http://pdfs.semanticscholar.org/20af/2edd8d1cb9f3874aee83a478c5af152298c0.pdf | archive-date = 20 February 2019 }}

Propranolol is a non-selective beta receptor antagonist. This means that it does not have preference to β₁ or β₂ receptors. It competes with sympathomimetic neurotransmitters for binding to receptors, which inhibits sympathetic stimulation of the heart. Blockage of neurotransmitter binding to β₁ receptors on cardiac myocytes inhibits activation of adenylate cyclase, which in turn inhibits cAMP synthesis leading to reduced Protein kinase A (PKA) activation. This results in less calcium influx to cardiac myocytes through voltage-gated L-type calcium channels meaning there is a decreased sympathetic effect on cardiac cells, resulting in antihypertensive effects including reduced heart rate and lower arterial blood pressure. Blockage of neurotransmitter binding to β₂ receptors on smooth muscle cells will increase contraction, which will increase hypertension.

Propranolol is rapidly and completely absorbed, with peak plasma levels achieved about 1–3 hours after ingestion. More than 90% of the drug is found bound to plasma protein in the blood. Coadministration with food appears to enhance bioavailability.{{cite book| vauthors = Rang HP |title=Rang & Dale's pharmacology|date=2011|publisher=Churchill Livingstone |location=Edinburgh |isbn=9780702034718 |page=106 |edition=7th }} Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment therefore increases its bioavailability. Propranolol can be absorbed along the whole intestine with the main absorption site being the colon,{{cite journal | vauthors = Nagare N, Damre A, Singh KS, Mallurwar SR, Iyer S, Naik A, Chintamaneni M | title = Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion | journal = Indian Journal of Pharmaceutical Sciences | volume = 72 | issue = 5 | pages = 625–629 | date = September 2010 | pmid = 21694996 | pmc = 3116309 | doi = 10.4103/0250-474X.78533 | doi-access = free }} which means people who have lost their colon due to surgery may absorb less propranolol. 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. Most of the metabolites are excreted in the urine.{{cite web |title=Propranolol |url=https://www.drugbank.ca/drugs/DB00571 |website=www.drugbank.ca |access-date=31 January 2019}}

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).{{cite web |title=Propranolol |url=https://pubchem.ncbi.nlm.nih.gov/compound/propranolol#section=Top |website=pubchem.ncbi.nlm.nih.gov |access-date=31 January 2019 |language=en}} Effective plasma concentrations are between 10 and 100 mg/L.{{Citation needed|date=September 2017}} Toxic levels are associated with plasma concentrations above 2000 mg/L.{{Citation needed|date=September 2017}}

{{Main|Discovery and development of β-adrenergic receptor antagonists (beta-blockers)}}

Scottish scientist James W. Black developed propranolol in the 1960s.{{cite journal | vauthors = Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC | title = A New Adrenergic Beta-Receptor Antagonist | journal = Lancet | volume = 1 | issue = 7342 | pages = 1080–1081 | date = May 1964 | pmid = 14132613 | doi = 10.1016/S0140-6736(64)91275-9 }} It was the first beta-blocker effectively used in the treatment of coronary artery disease and hypertension.{{Cite book|title=Basic & Clinical Pharmacology| vauthors = Benowitz NL |publisher=McGraw-Hill|year=2017|isbn=9781259641152| veditors = Katzung BG |edition=14th|chapter=Antihypertensive Agents}}

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

In a 1987 study by the International Conference of Symphony and Opera Musicians, it was reported that 27% of interviewed members said they used beta blockers such as propranolol for musical performances.{{cite journal |vauthors=Fishbein M, Middlestadt SE, Ottati V, Straus S, Ellis A | year = 1988 | title = Medical problems among ICSOM musicians: overview of a national survey | journal = Med Probl Perform Artist | volume = 3| pages = 1–8}} For about 10–16% of performers, their degree of stage fright is considered pathological.{{cite journal |vauthors=Steptoe A, Malik F, Pay C, Pearson P, Price C, Win Z | year = 1995 | title = The impact of stage fright on student actors | journal = Br J Psychol | volume = 86| pages = 27–39 | doi=10.1111/j.2044-8295.1995.tb02544.x}} Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.{{cite journal | vauthors = Lockwood AH | title = Medical problems of musicians | journal = The New England Journal of Medicine | volume = 320 | issue = 4 | pages = 221–227 | date = January 1989 | pmid = 2643048 | doi = 10.1056/nejm198901263200405 }} It has also been used as a performance-enhancing drug in sports where high accuracy is required, including archery, shooting, golf,{{cite news |author=Tim Glover |url=https://www.independent.co.uk/sport/golf-ogrady-says-players-use-betablockers-drugs-helped-win-majors-1368307.html |title=Golf: O'Grady says players use beta-blockers: Drugs 'helped win majors' |newspaper=The Independent |access-date=28 March 2017 |url-status=live |archive-url=https://web.archive.org/web/20150925223906/http://www.independent.co.uk/sport/golf-ogrady-says-players-use-betablockers-drugs-helped-win-majors-1368307.html |archive-date=25 September 2015 }} and snooker. In the 2008 Summer Olympics, 50-metre pistol silver medalist and 10-metre air pistol bronze medalist Kim Jong-su tested positive for propranolol and was stripped of his medals.{{cite web| vauthors = Scott M |title=Olympics: North Korea's Kim Jong-su loses medals after positive drugs test |url= https://www.theguardian.com/sport/2008/aug/15/olympics2008.drugsinsport |website=The Guardian |publisher=Guardian News and Media Limited |access-date=7 March 2018 |date=15 August 2008}}

Propranolol was first marketed under the brand name Inderal, manufactured by ICI Pharmaceuticals (now AstraZeneca), in 1965. "Inderal" is a quasi-anagram of "Alderlin", the trade name of pronethalol (which propranolol replaced); both names are an homage to Alderley Park, the ICI headquarters where the drugs were first developed.{{cite journal |vauthors=Quirke V |title=Putting theory into practice: James Black, receptor theory and the development of the beta-blockers at ICI, 1958-1978 |journal=Med Hist |volume=50 |issue=1 |pages=69–92 |date=January 2006 |pmid=16502872 |pmc=1369014 |doi=10.1017/s0025727300009455}}

Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok,{{Cite web |title=Indoblok Tablet - Product - TabletWise.com |url=https://www.tabletwise.com/southafrica/indoblok-tablet |access-date=15 October 2022 |website=www.tabletwise.com |language=en}} Sumial, Anaprilin, and Bedranol SR (Sandoz). In India, it is marketed under brand names such as Ciplar and Ciplar LA by Cipla. Hemangeol, a 4.28 mg/mL solution of propranolol, is indicated for the treatment of proliferating infantile hemangioma.{{cite web|title=Hemangeol - Food and Drug Administration|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205410s000lbl.pdf|access-date=23 March 2015|date=1 March 2014|url-status=live|archive-url=https://web.archive.org/web/20150402113709/https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205410s000lbl.pdf|archive-date=2 April 2015}}

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• {{cite journal | vauthors = Stapleton MP | title = Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology | journal = Texas Heart Institute Journal | volume = 24 | issue = 4 | pages = 336–342 | year = 1997 | pmid = 9456487 | pmc = 325477 }}

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