Propranolol Explained

Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors,[1] [2] as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks.[3] It can be taken orally (by mouth) or by intravenous injection (injection into a vein).[3] The formulation that is taken orally (by mouth) comes in short-acting and long-acting versions.[3] Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.[3] [4]

Common side effects include nausea, abdominal pain, and constipation.[3] It may worsen the symptoms of asthma.[3] Propranolol may cause harmful effects for the baby if taken during pregnancy.[5] Its use during breastfeeding is probably safe.[6] It is a non-selective beta blocker which works by blocking β-adrenergic receptors.[3]

Propranolol was patented in 1962 and approved for medical use in 1964.[7] It is on the World Health Organization's List of Essential Medicines.[8] Propranolol is available as a generic medication.[3] In 2021, it was the 91st most commonly prescribed medication in the United States, with more than 7million prescriptions.[9] [10]

Medical uses

Propranolol is used for treating various conditions, including:

Cardiovascular

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.[11]

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.[12]

Psychiatric

Propranolol is occasionally used to treat performance anxiety,[1] although evidence to support its use in any anxiety disorders is poor.[13] Its efficacy in managing panic disorder appears similar to benzodiazepines, while carrying lower risks for addiction or abuse.[13] 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.[14] Some experimentation has been conducted in other psychiatric areas:[15]

PTSD and phobias

Propranolol is being investigated as a potential treatment for PTSD.[19] [20] [21] Propranolol works to inhibit the actions of norepinephrine (noradrenaline), a neurotransmitter that enhances memory consolidation.[22] 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.[23] 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.[24]

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.[25] 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".[26]

Other uses

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.[32]

Contraindications

Propranolol may be contraindicated in people with:

Adverse effects

Propranolol should be used with caution in people with:[33]

Pregnancy and lactation

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.[34]

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.[35] 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".[34] [35] [36] [37]

Overdose

In overdose propranolol is associated with seizures.[38] Cardiac arrest may occur in propranolol overdose due to sudden ventricular arrhythmias, or cardiogenic shock which may ultimately culminate in bradycardic PEA.[39]

Interactions

Since beta blockers are known to relax the cardiac muscle and to constrict the smooth muscle, 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:

Pharmacology

Pharmacodynamics

Propranolol[41]
Site Ki (nM) Species Ref
55–272 Human [42] [43]
56–85 Rat [44] [45]
4,070 Pig [46]
4,280 Human [47]
457–513
166–316 		Human [48]
61,700
5,010
736–2,457 		Human
Human
Rodent

[49]
>10,000 Human [50]
1,297–2,789 Rat [51]
0.02–2.69 Human [52] [53]
0.01–0.61 Human
450 Mouse [54]
>10,000 Human
>10,000 Human
>10,000 Human [55]
3,700 Rat [56]
5,000 Rat [57]
29,000 Rat
>10,000 Rat [58]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

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;[59] 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).[60] Propranolol is able to cross the blood–brain barrier and exert effects in the central nervous system in addition to its peripheral activity.[13]

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).[61] [57] 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-HT1A, 5-HT1B, and 5-HT2B receptors.[62] [63] 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.[64] [65] [66]

Mechanism of action

Propranolol is a non-selective beta receptor antagonist.[59] 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 PKA (Protein Kinase A) 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.

Pharmacokinetics

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.[67] 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 colon,[68] which means people who have lost their colon due to surgery may absorb relatively less percentage of 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.[69]

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).[70] Effective plasma concentrations are between 10 and 100 mg/L. Toxic levels are associated with plasma concentrations above 2000 mg/L.

Idropranolol

Drug Name:Idropranolol
Iupac Name:1-(5,6-Dihydro-1-naphthalenyloxy)-3-(isopropylamino)-2-propanol
Legal Status:Never marketed
Atc Prefix:None
Cas Number:27581-02-8
Unii:5U6118QYHK
Pubchem:163314
Chemspiderid:143322
Chembl:1742463
C:16
H:23
N:1
O:2
Smiles:CC(C)NCC(COC1=CC=CC2=C1C=CCC2)O
Stdinchi:1S/C16H23NO2/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16/h4-5,7-9,12,14,17-18H,3,6,10-11H2,1-2H3
Stdinchikey:JKLYFQUDQSQWRB-UHFFFAOYSA-N

Idropranolol is a beta blocker, similar in structure to propranolol, that was never marketed.[71] [72]

History

See main article: Discovery and development of β-adrenergic receptor antagonists (beta-blockers).

Scottish scientist James W. Black developed propranolol in the 1960s.[73] It was the first beta-blocker effectively used in the treatment of coronary artery disease and hypertension.[74] In 1988, Black was awarded the Nobel Prize in Medicine for this discovery. Propranolol was inspired by the early β-adrenergic antagonists dichloroisoprenaline and pronethalol. The key difference, which was carried through to essentially all subsequent beta blockers, was the inclusion of an oxymethylene group (-O-CH2-) between the aryl and ethanolamine moieties of pronethalol, 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 bisoprolol, nebivolol, carvedilol, or metoprolol) are now used preferentially in the treatment of hypertension.

Society and culture

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.[75] For about 10–16% of performers, their degree of stage fright is considered pathological.[75] [76] Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.[77] It has also been used as a performance-enhancing drug in sports where high accuracy is required, including archery, shooting, golf,[78] and snooker.[78] 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.[79]

Brand names

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.[80]

Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok,[81] 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.[82]

Further reading

Notes and References

  1. Davidson JR . Pharmacotherapy of social anxiety disorder: what does the evidence tell us? . The Journal of Clinical Psychiatry . 67 . Suppl 12 . 20–26 . 2006 . 17092192 . 10.1016/j.genhosppsych.2005.07.002 .
  2. Chinnadurai S, Fonnesbeck C, Snyder KM, Sathe NA, Morad A, Likis FE, McPheeters ML . Pharmacologic Interventions for Infantile Hemangioma: A Meta-analysis . Pediatrics . 137 . 2 . e20153896 . February 2016 . 26772662 . 10.1542/peds.2015-3896 . 30459652 . free .
  3. Web site: Propranolol hydrochloride . Monograph . The American Society of Health-System Pharmacists . 1 January 2015 . live . https://web.archive.org/web/20150101152631/http://www.drugs.com/monograph/propranolol-hydrochloride.html . 1 January 2015 . dmy-all .
  4. Book: Bryson PD . Comprehensive review in toxicology for emergency clinicians. 1997. Taylor & Francis. Washington, DC. 9781560326120. 167. 3. live. https://web.archive.org/web/20170324020627/https://books.google.com/books?id=f7009NkJv70C&pg=PA167. 24 March 2017.
  5. Web site: Prescribing medicines in pregnancy database. Australian Government. 22 April 2014. 3 March 2014. live. https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw. 8 April 2014.
  6. Book: Briggs GG, Freeman RK, Yaffe SJ . Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 2011. Wolters Kluwer Health/Lippincott Williams & Wilkins . Philadelphia . 9781608317080 . 1226. 9th. live. https://web.archive.org/web/20170214212837/https://books.google.ca/books?id=OIgTE4aynrMC&pg=PA1226. 14 February 2017.
  7. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 460 .
  8. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO .
  9. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  10. Web site: Propranolol - Drug Usage Statistics . ClinCalc . 14 January 2024.
  11. Web site: Ladva S . NICE and BHS launch updated hypertension guideline . 28 June 2006 . . 11 October 2009 . https://web.archive.org/web/20060924003311/http://www.nice.org.uk/download.aspx?o=335988 . 24 September 2006 . dmy-all .
  12. 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 . 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) . JAMA . 311 . 5 . 507–520 . February 2014 . 24352797 . 10.1001/jama.2013.284427 . dmy-all . free .
  13. Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A . Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis . Journal of Psychopharmacology . 30 . 2 . 128–139 . February 2016 . 26487439 . 4724794 . 10.1177/0269881115612236 .
  14. Beta-blockers in anxiety disorders . Peggy H, Charles S . 10.1016/0165-0327(87)90017-6 . Journal of Affective Disorders . 13 . 2 . October 1987 . 119–130. 2890677 .
  15. Kornischka J, Cordes J, Agelink MW . 40 years beta-adrenoceptor blockers in psychiatry . de . Fortschritte der Neurologie-Psychiatrie . 75 . 4 . 199–210 . April 2007 . 17200914 . 10.1055/s-2006-944295 . 260156607 .
  16. Thibaut F, Colonna L . [Anti-aggressive effect of beta-blockers] . fr . L'Encephale . 19 . 3 . 263–267 . 1993 . 7903928 .
  17. Vieweg V, Pandurangi A, Levenson J, Silverman J . The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia . International Journal of Psychiatry in Medicine . 24 . 4 . 275–303 . 1994 . 7737786 . 10.2190/5WG5-VV1V-BXAD-805K . 22703210 .
  18. Kishi Y, Kurosawa H, Endo S . Is propranolol effective in primary polydipsia? . International Journal of Psychiatry in Medicine . 28 . 3 . 315–325 . 1998 . 9844835 . 10.2190/QPWL-14H7-HPGG-A29D . 25222454 .
  19. Web site: Doctors test a drug to ease traumatic memories - Mental Health - NBC News . https://web.archive.org/web/20131112233001/http://www.nbcnews.com/id/10806799/ . dead . 12 November 2013 . . 30 June 2007 .
  20. Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK . 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 . 503–506 . May 2008 . 17588604 . 10.1016/j.jpsychires.2007.05.006 .
  21. Book: Young C, Butcher R . Propranolol for Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness . 2020 . Canadian Agency for Drugs and Technologies in Health . CADTH Rapid Response Reports . Ottawa (ON) . 33074615.
  22. Web site: DocFilm – DW . 2 August 2023 . dw.com . en.
  23. Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR . Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma . Biological Psychiatry . 54 . 9 . 947–949 . November 2003 . 14573324 . 10.1016/s0006-3223(03)00412-8 . 3064619 .
  24. Webb J . β-Blockers for the Treatment of Misophonia and Misokinesia . Clinical Neuropharmacology . 45 . 1 . 13–14 . Jan–Feb 2022 . 35029865 . 10.1097/WNF.0000000000000492 . 245932937 .
  25. Kolber AJ . Therapeutic Forgetting: The Legal and Ethical Implications of Memory Dampening . Vanderbilt Law Review, San Diego Legal Studies Paper No. 07-37. . 59 . 1561 . 2006.
  26. Hall W, Carter A . Debunking alarmist objections to the pharmacological prevention of PTSD . The American Journal of Bioethics . 7 . 9 . 23–25 . September 2007 . 17849333 . 10.1080/15265160701551244 . 27063524 .
  27. Lima AR, Bacalcthuk J, Barnes TR, Soares-Weiser K . Central action beta-blockers versus placebo for neuroleptic-induced acute akathisia . The Cochrane Database of Systematic Reviews . 4 . CD001946 . October 2004 . 2004 . 15495022 . 6599862 . 10.1002/14651858.CD001946.pub2 .
  28. Shields KG, Goadsby PJ . Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine? . Brain . 128 . Pt 1 . 86–97 . January 2005 . 15574468 . 10.1093/brain/awh298 . free .
  29. Book: The Biochemistry of Migraine . Eadie M, Tyrer JH . 1985 . Springer . New York . 9780852007310 . 148 . 11726870 . live . 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 . 24 March 2017 .
  30. Web site: Chan C, Goadsby PJ . Silberstein SD . 26 September 1996 . Primary exercise headache . MedLink .
  31. Chen T, Gudipudi R, Nguyen SA, Carroll W, Clemmens C . Should Propranolol Remain the Gold Standard for Treatment of Infantile Hemangioma? A Systematic Review and Meta-Analysis of Propranolol Versus Atenolol . The Annals of Otology, Rhinology, and Laryngology . 332–340 . April 2022 . 132 . 3 . 35466712 . 10.1177/00034894221089758 . 248375711 .
  32. Current Dermatology Reports . 2012 . 10.1007/s13671-012-0026-6 . Propranolol for Infantile Hemangiomas: A Review . Hogeling M . Online-first . 1. 4 . free .
  33. Book: Rossi S . . 2006 . Adelaide . Australian Medicines Handbook .
  34. Book: Sweetman SC . Cardiovascular Drugs. Martindale: The complete drug reference . 36th . 2009. 1226–1381. Pharmaceutical Press . London. 978-0-85369-840-1. Martindale: The complete drug reference.
  35. No authors listed
  36. Committee on Drugs . Transfer of drugs and other chemicals into human milk . Pediatrics . 108 . 3 . 776–789 . September 2001 . 11533352 . 10.1542/peds.108.3.776. 27763768 . free .
  37. Spencer JP, Gonzalez LS, Barnhart DJ . Medications in the breast-feeding mother . American Family Physician . 64 . 1 . 119–126 . July 2001 . 11456429 .
  38. Reith DM, Dawson AH, Epid D, Whyte IM, Buckley NA, Sayer GP . Relative toxicity of beta blockers in overdose . Journal of Toxicology. Clinical Toxicology . 34 . 3 . 273–278 . 1996 . 8667464 . 10.3109/15563659609013789 .
  39. Holstege CP, Eldridge DL, Rowden AK . ECG manifestations: the poisoned patient . Emergency Medicine Clinics of North America . 24 . 1 . 159–77, vii . February 2006 . 16308118 . 10.1016/j.emc.2005.08.012 .
  40. van Harten J . Overview of the pharmacokinetics of fluvoxamine . Clinical Pharmacokinetics . 29 . Suppl 1 . 1–9 . 1995 . 8846617 . 10.2165/00003088-199500291-00003 . 71812133 .
  41. Web site: PDSP Ki Database . Psychoactive Drug Screening Program (PDSP). Bryan Roth . Roth BL, Driscol J . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 14 August 2017 .
  42. Hamon M, Lanfumey L, el Mestikawy S, Boni C, Miquel MC, Bolaños F, Schechter L, Gozlan H . The main features of central 5-HT1 receptors . Neuropsychopharmacology . 3 . 5–6 . 349–360 . 1990 . 2078271 .
  43. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS . Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications . NIDA Research Monograph . 178 . 440–466 . March 1998 . 9686407 .
  44. Tsuchihashi H, Nakashima Y, Kinami J, Nagatomo T . Characteristics of 125I-iodocyanopindolol binding to beta-adrenergic and serotonin-1B receptors of rat brain: selectivity of beta-adrenergic agents . Japanese Journal of Pharmacology . 52 . 2 . 195–200 . February 1990 . 1968985 . 10.1254/jjp.52.195 . free .
  45. Engel G, Göthert M, Hoyer D, Schlicker E, Hillenbrand K . Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites . Naunyn-Schmiedeberg's Archives of Pharmacology . 332 . 1 . 1–7 . January 1986 . 2936965 . 10.1007/bf00633189 . 5999838 .
  46. Schlicker E, Fink K, Göthert M, Hoyer D, Molderings G, Roschke I, Schoeffter P . The pharmacological properties of the presynaptic serotonin autoreceptor in the pig brain cortex conform to the 5-HT1D receptor subtype . Naunyn-Schmiedeberg's Archives of Pharmacology . 340 . 1 . 45–51 . July 1989 . 2797214 . 10.1007/bf00169206 . 2287040 .
  47. Elliott JM, Kent A . Comparison of [125I]iodolysergic acid diethylamide binding in human frontal cortex and platelet tissue . Journal of Neurochemistry . 53 . 1 . 191–196 . July 1989 . 2723656 . 10.1111/j.1471-4159.1989.tb07313.x . 25820829 .
  48. Schmuck K, Ullmer C, Kalkman HO, Probst A, Lubbert H . Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache? . The European Journal of Neuroscience . 8 . 5 . 959–967 . May 1996 . 8743744 . 10.1111/j.1460-9568.1996.tb01583.x . 19578349 .
  49. Yagaloff KA, Hartig PR . 125I-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells . The Journal of Neuroscience . 5 . 12 . 3178–3183 . December 1985 . 4078623 . 6565215 . 10.1523/JNEUROSCI.05-12-03178.1985 .
  50. Barnes JM, Barnes NM, Costall B, Ironside JW, Naylor RJ . Identification and characterisation of 5-hydroxytryptamine 3 recognition sites in human brain tissue . Journal of Neurochemistry . 53 . 6 . 1787–1793 . December 1989 . 2809591 . 10.1111/j.1471-4159.1989.tb09244.x . 46356673 .
  51. Boyajian CL, Leslie FM . Pharmacological evidence for alpha-2 adrenoceptor heterogeneity: differential binding properties of [3H]rauwolscine and [3H]idazoxan in rat brain . The Journal of Pharmacology and Experimental Therapeutics . 241 . 3 . 1092–1098 . June 1987 . 2885406 .
  52. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE . Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding . Psychopharmacology . 124 . 1–2 . 57–73 . March 1996 . 8935801 . 10.1007/bf02245606 . 12028979 .
  53. Fraundorfer PF, Fertel RH, Miller DD, Feller DR . Biochemical and pharmacological characterization of high-affinity trimetoquinol analogs on guinea pig and human beta adrenergic receptor subtypes: evidence for partial agonism . The Journal of Pharmacology and Experimental Therapeutics . 270 . 2 . 665–674 . August 1994 . 7915318 .
  54. Nahmias C, Blin N, Elalouf JM, Mattei MG, Strosberg AD, Emorine LJ . Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes . The EMBO Journal . 10 . 12 . 3721–3727 . December 1991 . 1718744 . 453106 . 10.1002/j.1460-2075.1991.tb04940.x .
  55. Kanba S, Richelson E . Histamine H1 receptors in human brain labelled with [3H]doxepin . Brain Research . 304 . 1 . 1–7 . June 1984 . 6146381 . 10.1016/0006-8993(84)90856-4 . 45303586 .
  56. Kovachich GB, Aronson CE, Brunswick DJ, Frazer A . Quantitative autoradiography of serotonin uptake sites in rat brain using [3H]cyanoimipramine . Brain Research . 454 . 1–2 . 78–88 . June 1988 . 2970277 . 10.1016/0006-8993(88)90805-0 . 9586842 .
  57. Tuross N, Patrick RL . Effects of propranolol on catecholamine synthesis and uptake in the central nervous system of the rat . The Journal of Pharmacology and Experimental Therapeutics . 237 . 3 . 739–745 . June 1986 . 2872325 .
  58. Zobrist RH, Mecca TE . [3H]TA-3090, a selective benzothiazepine-type calcium channel receptor antagonist: in vitro characterization . The Journal of Pharmacology and Experimental Therapeutics . 253 . 2 . 461–465 . May 1990 . 2338642 .
  59. Book: Al-Majed AA, Bakheit AH, Abdel Aziz HA, Alajmi FM, AlRabiah H . Propranolol . Profiles of Drug Substances, Excipients, and Related Methodology . Profiles of Drug Substances, Excipients and Related Methodology . 42 . 287–338 . 2017 . 28431779 . 10.1016/bs.podrm.2017.02.006 . 9780128122266 .
  60. Book: Naish J, Court DS . Medical sciences. 2014. 978-0702052491. 150. Elsevier Health Sciences . Second.
  61. Young R, Glennon RA . S(-)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats . Psychopharmacology . 203 . 2 . 369–382 . April 2009 . 18795268 . 10.1007/s00213-008-1317-2 . free .
  62. Davids E, Lesch KP . [The 5-HT1A receptor: a new effective principle in psychopharmacologic therapy?] . de . Fortschritte der Neurologie-Psychiatrie . 64 . 11 . 460–472 . November 1996 . 9064274 . 10.1055/s-2007-996592 . 147793142 .
  63. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP . International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin) . Pharmacological Reviews . 46 . 2 . 157–203 . June 1994 . 7938165 .
  64. Wang DW, Mistry AM, Kahlig KM, Kearney JA, Xiang J, George AL . Propranolol blocks cardiac and neuronal voltage-gated sodium channels . Frontiers in Pharmacology . 1 . 144 . 2010 . 21833183 . 3153018 . 10.3389/fphar.2010.00144 . free .
  65. Bankston JR, Kass RS . Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3 . Journal of Molecular and Cellular Cardiology . 48 . 1 . 246–253 . January 2010 . 19481549 . 2813422 . 10.1016/j.yjmcc.2009.05.012 .
  66. Desaphy JF, Pierno S, De Luca A, Didonna P, Camerino DC . Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders . Molecular Pharmacology . 63 . 3 . 659–670 . March 2003 . 12606775 . 10.1124/mol.63.3.659 . 631197 . https://web.archive.org/web/20190220073326/http://pdfs.semanticscholar.org/20af/2edd8d1cb9f3874aee83a478c5af152298c0.pdf . 20 February 2019 .
  67. Book: Rang HP . Rang & Dale's pharmacology. 2011. Churchill Livingstone . Edinburgh . 9780702034718 . 106 . 7th .
  68. Nagare N, Damre A, Singh KS, Mallurwar SR, Iyer S, Naik A, Chintamaneni M . Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion . Indian Journal of Pharmaceutical Sciences . 72 . 5 . 625–629 . September 2010 . 21694996 . 3116309 . 10.4103/0250-474X.78533 . free .
  69. Web site: Propranolol . www.drugbank.ca . 31 January 2019.
  70. Web site: Propranolol . pubchem.ncbi.nlm.nih.gov . 31 January 2019 . en.
  71. Book: Concise Dictionary of Pharmacological Agents: Properties and Synonyms . Morton IK, Hall JM . Springer . Oct 31, 1999 . 150.
  72. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 676.
  73. Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC . A New Adrenergic Beta-Receptor Antagonist . Lancet . 1 . 7342 . 1080–1081 . May 1964 . 14132613 . 10.1016/S0140-6736(64)91275-9 .
  74. Book: Basic & Clinical Pharmacology. Benowitz NL . McGraw-Hill. 2017. 9781259641152. Katzung BG . 14th. Antihypertensive Agents.
  75. 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.
  76. 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 . 10.1111/j.2044-8295.1995.tb02544.x.
  77. Lockwood AH . Medical problems of musicians . The New England Journal of Medicine . 320 . 4 . 221–227 . January 1989 . 2643048 . 10.1056/nejm198901263200405 .
  78. News: Tim Glover . Golf: O'Grady says players use beta-blockers: Drugs 'helped win majors' . . 28 March 2017 . live . https://web.archive.org/web/20150925223906/http://www.independent.co.uk/sport/golf-ogrady-says-players-use-betablockers-drugs-helped-win-majors-1368307.html . 25 September 2015 .
  79. Web site: Scott M . Olympics: North Korea's Kim Jong-su loses medals after positive drugs test . The Guardian . Guardian News and Media Limited . 7 March 2018 . 15 August 2008.
  80. Quirke V . Putting theory into practice: James Black, receptor theory and the development of the beta-blockers at ICI, 1958-1978 . Med Hist . 50 . 1 . 69–92 . January 2006 . 16502872 . 1369014 . 10.1017/s0025727300009455.
  81. Web site: Indoblok Tablet - Product - TabletWise.com . 15 October 2022 . www.tabletwise.com . en.
  82. Web site: Hemangeol - Food and Drug Administration. 23 March 2015. 1 March 2014. live. https://web.archive.org/web/20150402113709/https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205410s000lbl.pdf. 2 April 2015.

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