View source for Isoprenaline

{{Short description|Medication for slow heart rate}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Watchedfields = verified
| verifiedrevid = 477495291
| image = Isoprenaline.svg
| width = 225px

<!-- Clinical data -->
| tradename = Isuprel, many others<ref name="IndexNominum2004" /><ref name="Drugs.com" />
| Drugs.com = {{drugs.com|monograph|isoproterenol}}
| MedlinePlus = a601236
| pregnancy_AU = A
| legal_AU = S4
| pregnancy_US = C
| legal_status = Rx-only
| routes_of_administration = [[Intravenous infusion|Intravenous]], [[intramuscular injection]], [[subcutaneous injection]], [[intracardiac injection]], [[inhalational administration|inhalation]], [[sublingual administration]], [[rectal administration]]<ref name="DrugBank" /><ref name="Drugs@FDA">{{cite web | title=Drugs@FDA: FDA-Approved Drugs | website=accessdata.fda.gov | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm | access-date=31 July 2024}}</ref>

<!-- Pharmacokinetic data -->
| bioavailability = [[Oral administration|Oral]]: Very low<ref name="Waldeck2002" /><ref name="ConollyDaviesDollery1972" />
| protein_bound = 69% (mostly to [[human serum albumin|albumin]])<ref name="DrugBank" />
| metabolism = [[Methylation]] ({{Abbrlink|COMT|Catechol O-methyltransferase}}), [[conjugation (biochemistry)|conjugation]] ([[sulfation]])<ref name="Morgan1990" /><ref name="DrugBank" />
| metabolites = • 3-''O''-Methylisoprenaline<ref name="DrugBank" /><br />• [[Sulfate]] [[conjugation (biochemistry)|conjugate]]s<ref name="Morgan1990" />
| onset = [[Inhalational administration|Inhalation]]: 2–5{{nbsp}}min<ref name="Sterling1995" />
| elimination_half-life = {{Abbrlink|IV|Intravenous infusion}}: 2.5–5{{nbsp}}min<ref name="DrugBank">{{cite web | title=Isoprenaline: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=19 February 1948 | url=https://go.drugbank.com/drugs/DB01064 | access-date=31 July 2024}}</ref><br />[[Oral administration|Oral]]: 40{{nbsp}}min<ref name="DrugBank" />
| duration_of_action = [[Inhalational administration|Inhalation]]: 0.5–2{{nbsp}}hours<ref name="Sterling1995" />
| excretion = [[Urine]]: 59–107%<ref name="DrugBank" /><br />[[Feces]]: 12–27%<ref name="DrugBank" />

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 7683-59-2
| ATC_prefix = C01
| ATC_suffix = CA02
| ATC_supplemental = {{ATC|R03|AB02}}<br />{{ATC|R03|CB01}}
| PubChem = 3779
| IUPHAR_ligand = 536
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01064
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3647
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = L628TT009W
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08090
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 434
| synonyms = Isoproterenol; Isopropylnorepinephrine; Isopropylnoradrenaline; Isopropydine; WIN-5162

<!-- Chemical data -->
| IUPAC_name = 4-[1-hydroxy-2-(isopropylamino)ethyl]benzene-1,2-diol
| C=11 | H=17 | N=1 | O=3
| SMILES = CC(C)NCC(O)c1cc(O)c(O)cc1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H17NO3/c1-7(2)12-6-11(15)8-3-4-9(13)10(14)5-8/h3-5,7,11-15H,6H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JWZZKOKVBUJMES-UHFFFAOYSA-N
}}
<!-- Definition and medical uses -->
'''Isoprenaline''', also known as '''isoproterenol''' and sold under the brand name '''Isuprel''' among others, is a [[sympathomimetic]] [[medication]] which is used in the treatment of acute [[bradycardia]] (slow heart rate), [[heart block]], and rarely for [[asthma]], among other indications.<ref name="Isuprel-Label">{{cite web|title=Label: Isoproterenol hydrochloride injection, solution|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a58f95fa-18f9-4938-8e3f-f33244f68298|publisher=NIH DailyMed|access-date=June 21, 2017|date=September 10, 2013}}</ref> It is used by [[intravenous administration|injection into a vein]], [[intramuscular injection|muscle]], [[subcutaneous injection|fat]], or the [[intracardiac injection|heart]], by [[inhalational administration|inhalation]], and in the past [[sublingual administration|under the tongue]] or [[rectal administration|into the rectum]].<ref name="DrugBank" /><ref name="Drugs@FDA" />

<!-- Side effects, mechanism, and chemistry -->
[[Side effect]]s of isoprenaline include [[tachycardia|rapid heart beat]], [[palpitation|heart palpitation]]s, and [[arrhythmia]]s, among others.<ref name="Isuprel-Label" /> Isoprenaline is a [[binding selectivity|selective]] [[agonist]] of the [[β-adrenergic receptor]]s, including both the [[β1-adrenergic receptor|β<sub>1</sub>-]] and [[β2-adrenergic receptor|β<sub>2</sub>-adrenergic receptor]]s.<ref name="Isuprel-Label" /> By activating these [[receptor (biochemistry)|receptor]]s, it increases [[heart rate]] and the [[myocardial contractility|force of heart contraction]]s.<ref name="MotwaniSaunders2024">{{cite journal | vauthors = Motwani SK, Saunders H | title=Inotropes | journal=Anaesthesia & Intensive Care Medicine | volume=25 | issue=3 | date=2024 | doi=10.1016/j.mpaic.2023.11.019 | pages=185–191}}</ref> Chemically, isoprenaline is a [[synthetic compound|synthetic]] [[catecholamine]] and is the ''N''-[[isopropyl]] [[structural analogue|analogue]] of [[norepinephrine]] (noradrenaline) and [[epinephrine]] (adrenaline).<ref name="PubChem" /><ref name="DrugBank" /><ref name="ChemSpider" /><ref name="Konzett1981" />

<!-- History, society, and culture -->
Isoprenaline was one of the first [[synthetic compound|synthetic]] [[sympathomimetic]] [[amine]]s and was the first [[binding selectivity|selective]] β-adrenergic receptor agonist.<ref name="Morgan1990" /><ref name="RuženaJindraRenáta2020" /> The medication was discovered in 1940<ref name="Waldeck2002" /> and was introduced for medical use in 1947.<ref name="MozayaniRaymon2003" />

==Medical uses==
Isoprenaline is used to treat [[heart block]] and episodes of [[Adams–Stokes syndrome]] that are not caused by [[ventricular tachycardia]] or [[fibrillation]], in emergencies for [[cardiac arrest]] until [[defibrillation|electric shock]] can be administered, for [[bronchospasm]] occurring during [[anesthesia]], and as an [[adjunct therapy|adjunct]] in the treatment of [[hypovolemic shock]], [[septic shock]], low [[cardiac output]] ([[hypoperfusion]]) states, [[congestive heart failure]], and [[cardiogenic shock]].<ref name="Isuprel-Label" /> It is also used to prevent [[Torsades de Pointes]] in patients with [[long QT]] refractory to [[magnesium]] and to treat patients with intermittent Torsades de Pointes refractory to treatment with magnesium.<ref name="Cohagan2022">{{cite book | vauthors = Cohagan B, Brandis D | chapter = Torsade de Pointes | date = August 2022 | title = StatPearls | location = Treasure Island (FL) | publisher = StatPearls Publishing |id={{NCBIBook2|NBK459388}} |pmid=29083738 }}</ref> Isoprenaline is used in the acute management of bradycardia, though not in the chronic treatment of bradycardia.<ref name="KusumotoSchoenfeldBarrett2019">{{cite journal | vauthors = Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, Goldschlager NF, Hamilton RM, Joglar JA, Kim RJ, Lee R, Marine JE, McLeod CJ, Oken KR, Patton KK, Pellegrini CN, Selzman KA, Thompson A, Varosy PD | title = 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society | journal = Circulation | volume = 140 | issue = 8 | pages = e382–e482 | date = August 2019 | pmid = 30586772 | doi = 10.1161/CIR.0000000000000628 | url = }}</ref>

Historically, it was used to treat [[asthma]] via metered aerosol or nebulizing devices; it was also available in sublingual, oral, intravenous, and intramuscular formulations.<ref name="MozayaniRaymon2003" /> The U.S. National Asthma Education and Prevention Program Expert Panel recommends against its use as a nebulizer for acute bronchoconstriction.<ref name="NAEPP2007">{{cite web|last1=National Asthma Education and Prevention Program Expert Panel |title= Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma |url= https://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf |publisher=NIH National Heart, Lung, and Blood Institute|date=August 28, 2007}}</ref>

===Available forms===
Many formulations of isoprenaline appear to have been discontinued in the [[United States]] and many other countries.<ref name="Drugs@FDA" /><ref name="IndexNominum2004" /><ref name="Drugs.com" /><ref name="DrugBank" /> In the United States, it remains available only as an [[injection (medicine)|injectable]] [[Solution (chemistry)|solution]].<ref name="Drugs@FDA" /> It was previously also available in the United States as a solution, metered [[aerosol]], powder, or disc for [[inhalational administration|inhalation]] and as a [[tablet (pharmacy)|tablet]] for [[sublingual administration|sublingual]] and [[rectal administration]], but these formulations were discontinued.<ref name="Drugs@FDA" />

==Contraindications==
It should not be used in people with [[tachyarrhythmia]]s (except in special circumstances),<ref name="JongmanJepkes-BruinRamdat2007">{{cite journal | vauthors = Jongman JK, Jepkes-Bruin N, Ramdat Misier AR, Beukema WP, Delnoy PP, Oude Lutttikhuis H, Dambrink JH, Hoorntje JC, Elvan A | title = Electrical storms in Brugada syndrome successfully treated with isoproterenol infusion and quinidine orally | journal = Netherlands Heart Journal | volume = 15 | issue = 4 | pages = 151–155 | date = April 2007 | pmid = 17612676 | pmc = 1847769 | doi = 10.1007/BF03085972 }}</ref> [[tachycardia]] or [[heart block]] caused by [[digitalis]] poisoning, [[ventricular arrhythmia]]s which require [[Inotrope#Positive inotropic agents|inotropic]] therapy, or with [[angina]].<ref name="Isuprel-Label" />

==Side effects==
[[Side effect]]s of isoprenaline may include [[nervousness]], [[headache]], [[dizziness]], [[nausea]], [[blurred vision]], [[tachycardia]], [[palpitations]], [[angina]], [[Adams–Stokes syndrome|Adams-Stokes attack]]s, [[pulmonary edema]], [[hypertension]], [[hypotension]], [[ventricular arrhythmia]]s, [[tachyarrhythmia]]s, [[difficulty breathing]], [[sweating]], mild [[tremor]]s, [[weakness]], [[flushing (physiology)|flushing]], and [[pallor]].<ref name="Isuprel-Label" /> Isoprenaline has been reported to cause [[insulin resistance]] leading to [[diabetic ketoacidosis]].<ref name="HoffKoh2018">{{cite journal | vauthors = Hoff R, Koh CK | title = Isoproterenol Induced Insulin Resistance Leading to Diabetic Ketoacidosis in Type 1 Diabetes Mellitus | journal = Case Reports in Endocrinology | volume = 2018 | pages = 4328954 | date = 2018 | pmid = 30647979 | pmc = 6311779 | doi = 10.1155/2018/4328954 | doi-access = free }}</ref>

==Overdose==
[[Overdose]] of isoprenaline may produce effects including [[tachycardia]], [[arrhythmia]]s, [[palpitation]]s, [[angina]], [[hypotension]], [[hypertension]], and [[cardiovascular disease|myocardial necrosis]].<ref name="DrugBank" /><ref name="Isuprel-Label" />

==Pharmacology==
===Pharmacodynamics===
Isoprenaline is a [[beta-1 adrenergic receptor|β<sub>1</sub>-]] and [[beta-2 adrenergic receptor|β<sub>2</sub>-adrenergic receptor]] [[full agonist]] and has almost no [[biological activity|activity]] at the [[alpha adrenergic receptor|α-adrenergic receptor]]s at lower concentrations.<ref name="MozayaniRaymon2003" /><ref name="EmilienMaloteaux1998">{{cite journal | vauthors = Emilien G, Maloteaux JM | title = Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists | journal = Eur J Clin Pharmacol | volume = 53 | issue = 6 | pages = 389–404 | date = February 1998 | pmid = 9551698 | doi = 10.1007/s002280050399 | url = }}</ref> It has similar [[affinity (pharmacology)|affinity]] for the β<sub>1</sub>- and β<sub>2</sub>-adrenergic receptors.<ref name="EmilienMaloteaux1998" /><ref name="Sterling1995">{{cite journal | vauthors = Sterling LP | title = Beta adrenergic agonists | journal = AACN Clin Issues | volume = 6 | issue = 2 | pages = 271–278 | date = May 1995 | pmid = 7743429 | doi = 10.1097/00044067-199505000-00010 | url = }}</ref> At higher concentrations, isoprenaline can also evoke responses mediated by α-adrenergic receptors.<ref name="Sterling1995" /><ref name="FurchgottBhadrakom1953">{{cite journal | vauthors = Furchgott RF, Bhadrakom S | title = Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 108 | issue = 2 | pages = 129–143 | date = June 1953 | pmid = 13062084 | url = https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=13062084 }}</ref><ref name="CopikBaldysNguyen2015">{{cite journal | vauthors = Copik AJ, Baldys A, Nguyen K, Sahdeo S, Ho H, Kosaka A, Dietrich PJ, Fitch B, Raymond JR, Ford AP, Button D, Milla ME | title = Isoproterenol acts as a biased agonist of the alpha-1A-adrenoceptor that selectively activates the MAPK/ERK pathway | journal = PLOS ONE | volume = 10 | issue = 1 | pages = e0115701 | date = 21 January 2015 | pmid = 25606852 | pmc = 4301629 | doi = 10.1371/journal.pone.0115701 | bibcode = 2015PLoSO..1015701C | doi-access = free }}</ref> Its agonist effects at the [[trace amine-associated receptor 1]] (TAAR1) additionally provide it with [[pharmacodynamic]] effects that resemble those of the endogenous [[trace amine]]s, like [[tyramine]].<ref name="KleinauPratzkaNürnberg2011">{{cite journal | vauthors = Kleinau G, Pratzka J, Nürnberg D, Grüters A, Führer-Sakel D, Krude H, Köhrle J, Schöneberg T, Biebermann H | title = Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists | journal = PLOS ONE | volume = 6 | issue = 10 | pages = e27073 | date = October 2011 | pmid = 22073124 | pmc = 3205048 | doi = 10.1371/journal.pone.0027073 | doi-access = free | bibcode = 2011PLoSO...627073K | quote = Table 1. EC50 values of different agonists at hTAAR1, hADRB1 and hADRB2 }}</ref>

Isoprenaline's effects on the [[cardiovascular system]] (non-selective) relate to its actions on [[heart|cardiac]] β<sub>1</sub>-adrenergic receptors and β<sub>2</sub>-adrenergic receptors on [[smooth muscle]] within the [[tunica media]] of [[arteriole]]s. Isoprenaline has [[Inotrope#Positive inotropic agents|positive inotropic]] and [[chronotropic]] effects on the heart. β<sub>2</sub>-Adrenergic receptor stimulation in [[arteriole|arteriolar]] smooth muscle induces [[vasodilation]]. Its inotropic and chronotropic effects elevate [[systole|systolic]] [[blood pressure]], while its vasodilatory effects tend to lower [[diastole|diastolic]] blood pressure. The overall effect is to decrease [[mean arterial pressure]] due to the vasodilation caused by β<sub>2</sub>-adrenergic receptor activation.<ref name="Korbut2017">{{cite book| vauthors = Korbut R |title=Farmakologia|date=2017|publisher=Wydawnictwo Lekarskie PZWL|isbn=978-83-200-5368-5|page=36|language=pl}}</ref>

The [[isopropylamine]] group in isoprenaline makes it selective for β-adrenergic receptors.<ref name="Mehta2011" />

The adverse effects of isoprenaline are also related to the drug's [[cardiovascular]] effects. Isoprenaline can produce [[tachycardia]] (an elevated [[heart rate]]), which predisposes people who take it to [[cardiac arrhythmia]]s.<ref name="MozayaniRaymon2003" />

===Pharmacokinetics===
====Absorption====
Data on the [[absorption (pharmacokinetics)|absorption]] of isoprenaline are limited.<ref name="DrugBank" /> [[Oral administration|Oral]] isoprenaline is [[absorption (pharmacokinetics)|well-absorbed]] but is subject to strong [[first-pass metabolism]]<ref name="George1981" /> and is approximately 1,000{{nbsp}}times less [[potency (pharmacology)|potent]] than [[intravenous administration]].<ref name="ConollyDaviesDollery1972" /> Hence, its oral [[bioavailability]] is very low.<ref name="Waldeck2002" /><ref name="ConollyDaviesDollery1972" /> Another study suggested that its oral bioavailability, based on [[pharmacodynamic]] activity via different routes, was slightly less than 4%.<ref name="George1981">{{cite journal | vauthors = George CF | title = Drug metabolism by the gastrointestinal mucosa | journal = Clin Pharmacokinet | volume = 6 | issue = 4 | pages = 259–274 | date = 1981 | pmid = 6113909 | doi = 10.2165/00003088-198106040-00002 | url = }}</ref><ref name="Redwood1969">{{cite journal | vauthors = Redwood D | title = Conservative treatment of chronic heart block | journal = Br Med J | volume = 1 | issue = 5635 | pages = 26–29 | date = January 1969 | pmid = 5761891 | pmc = 1981820 | doi = 10.1136/bmj.1.5635.26 | url = }}</ref>

====Distribution====
Isoprenaline is minimally able to cross the [[blood–brain barrier]] and hence is a [[peripherally selective drug]].<ref name="OlesenHougårdHertz1978">{{cite journal | vauthors = Olesen J, Hougård K, Hertz M | title = Isoproterenol and propranolol: ability to cross the blood-brain barrier and effects on cerebral circulation in man | journal = Stroke | volume = 9 | issue = 4 | pages = 344–349 | date = 1978 | pmid = 209581 | doi = 10.1161/01.str.9.4.344 | url = | quote = Mean extraction of isoproterenol in a single passage of the brain circulation was 3.8% and the calculated PS product was 2.0 ml/100g/min. The mean extraction of propranolol was 63.0% and the mean PS product 46.7 ml/100 g/min. [...] Passage of Isoproterenol and Propranolol Across Blood–Brain Barrier: No data are available in the literature concerning the ability of isoproterenol to cross the blood-brain barrier. From the hydrophilic nature of the molecule one might expect diffusion to be very slow, but the possibility of active uptake mechanisms still existed. The extraction of 3.8% found in the present study corresponds to that of sodium or other hydrophilic molecules.12 It is likely that a significant part of this extraction stems from areas known to be devoid of a blood-brain barrier. The extraction is clearly much smaller than that seen for amino acids and other substances that pass the barrier by facilitated diffusion.14}}</ref><ref name="CrystalSalem2002">{{cite journal | vauthors = Crystal GJ, Salem MR | title = Beta-adrenergic stimulation restores oxygen extraction reserve during acute normovolemic hemodilution | journal = Anesth Analg | volume = 95 | issue = 4 | pages = 851–857, table of contents | date = October 2002 | pmid = 12351256 | doi = 10.1097/00000539-200210000-00011 | url = | quote = The lack of effect of blood-borne catecholamines, including isoproterenol, on cerebral blood flow has been attributed to their inability to cross the blood-brain barrier (26).}}</ref> This is attributed to its high [[hydrophilicity]].<ref name="OlesenHougårdHertz1978" /> Whereas the extraction of isoprenaline in a single passage of the brain circulation following [[intravenous injection]] in humans was 3.8%, the extraction of propranolol, which is a more [[lipophilic]] compound and is readily able to cross into the brain, was 63.0%.<ref name="OlesenHougårdHertz1978" />

The [[plasma protein binding]] of isoprenaline is 68.8 ± 1.2%.<ref name="DrugBank" /> It is bound mainly to [[human serum albumin|albumin]].<ref name="DrugBank" />

====Metabolism====
Isoprenaline is [[metabolism|metabolized]] by [[catechol O-methyltransferase|catechol ''O''-methyltransferase]] (COMT) and [[conjugation (biochemistry)|conjugation]] by [[sulfation]].<ref name="Morgan1990" /><ref name="ProcacciniSawyerWatt2019">{{cite book |doi=10.1016/B978-1-4557-0760-7.00019-X |chapter=Pharmacology of Cardiovascular Drugs |title=Critical Heart Disease in Infants and Children |year=2019 | vauthors = Procaccini DE, Sawyer JE, Watt KM |pages=192–212.e6 |isbn=978-1-4557-0760-7 |s2cid=81053428 }}</ref><ref name="Szymanski2022">{{cite book | vauthors = Szymanski MW, Singh DP |chapter=Isoproterenol |title=StatPearls |date=2023 |publisher=StatPearls Publishing |id={{NCBIBook2|NBK526042}} |pmid=30252298 }}</ref><ref name="DrugBank" /> It does not appear to be [[glucuronidation|glucuronidated]].<ref name="Morgan1990" /> There is very large [[interindividual variability]] in the sulfation of isoprenaline.<ref name="Morgan1990" /> The free [[catechol]] [[hydroxyl]] groups keep it susceptible to enzymatic metabolism.<ref name="Mehta2011">{{cite web| vauthors = Mehta A |title=Notes - Medicinal Chemistry of the Peripheral Nervous System - Adrenergics and Cholinergic |url= http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html |publisher=Pharmaxchange |access-date=June 21, 2017 |date=January 27, 2011|archive-url= https://web.archive.org/web/20101104022742/http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html|archive-date=4 November 2010|url-status=dead}}</ref> The drug is a poor [[substrate (biochemistry)|substrate]] for [[monoamine oxidase]] (MAO) and is not metabolized by this enzyme.<ref name="Morgan1990" /><ref name="Isuprel-Label" /> This is in contrast to [[epinephrine]] and [[norepinephrine]].<ref name="Morgan1990" /> Isoprenaline is much more strongly metabolized and conjugated with oral administration than with intravenous administration.<ref name="ConollyDaviesDollery1972" /> Its [[metabolite]] 3-''O''-methylisoprenaline, formed by COMT, is [[biological activity|active]] as a weak [[beta blocker|β-adrenergic receptor antagonist]].<ref name="Morgan1990" />

====Elimination====
Isoprenaline is [[excretion|excreted]] primarily in the [[urine]], as [[sulfate]] [[conjugation (biochemistry)|conjugate]]s.<ref name="Morgan1990" /><ref name="ProcacciniSawyerWatt2019" /><ref name="Szymanski2022" /><ref name="DrugBank" /> It is excreted 59 to 107% in urine and 12 to 27% in [[feces]].<ref name="DrugBank" /> A majority of isoprenaline is excreted in urine in conjugated form, whereas 6.5 to 16.2% is excreted as unchanged isoprenaline and 2.6 to 11.4% is excreted as 3-O-methylisoprenaline and conjugates.<ref name="DrugBank" /><ref name="ConollyDaviesDollery1972" /> 

The [[elimination half-life]] of isoprenaline by [[intravenous administration]] is approximately 2.5 to 5{{nbsp}}minutes.<ref name="DrugBank" /> Its half-life with [[oral administration]] is approximately 40{{nbsp}}minutes.<ref name="DrugBank" /><ref name="ConollyDaviesDollery1972">{{cite journal | vauthors = Conolly ME, Davies DS, Dollery CT, Morgan CD, Paterson JW, Sandler M | title = Metabolism of isoprenaline in dog and man | journal = Br J Pharmacol | volume = 46 | issue = 3 | pages = 458–472 | date = November 1972 | pmid = 4656607 | pmc = 1666503 | doi = 10.1111/j.1476-5381.1972.tb08143.x | url = }}</ref>

==Chemistry==
Isoprenaline, also known as ''N''-isopropyl-3,4,β-trihydroxyphenethylamine or as ''N''-isopropylnorepinephrine, is a [[substituted phenethylamine]] and [[synthetic compound|synthetic]] [[catecholamine]] [[chemical derivative|derivative]].<ref name="PubChem">{{cite web | title=Isoproterenol | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/3779 | access-date=31 July 2024}}</ref><ref name="DrugBank" /><ref name="ChemSpider">{{cite web | title=Isoprenaline | website=ChemSpider | date=21 July 2022 | url=https://www.chemspider.com/Chemical-Structure.3647.html | access-date=31 July 2024}}</ref><ref name="Isuprel-Label" /> It is the ''N''-[[isopropyl]] [[structural analogue|analogue]] of [[norepinephrine]] (3,4,β-trihydroxyphenethylamine) and [[epinephrine]] (3,4,β-trihydroxy-''N''-methylphenethylamine).<ref name="PubChem" /><ref name="Konzett1981">{{cite journal | vauthors = Konzett H | title=On the discovery of isoprenaline | journal=Trends in Pharmacological Sciences | volume=2 | date=1981 | doi=10.1016/0165-6147(81)90259-5 | pages=47–49}}</ref>

Isoprenaline is a [[small-molecule]] [[chemical compound|compound]] with the [[molecular formula]] C<sub>11</sub>H<sub>17</sub>NO<sub>3</sub> and a [[molecular weight]] of 211.26{{nbsp}}g/mol.<ref name="PubChem" /><ref name="DrugBank" /><ref name="ChemSpider" /><ref name="Isuprel-Label" /> It is a [[hydrophilic]] compound<ref name="OlesenHougårdHertz1978" /> with a predicted [[partition coefficient|log P]] of -0.6 to 0.25.<ref name="PubChem" /><ref name="DrugBank" /><ref name="ChemSpider" /> For comparison, the experimental log P values of epinephrine and norepinephrine are -1.37 and -1.24, respectively.<ref name="PubChem-Epinephrine">{{cite web | title=Epinephrine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/5816 | access-date=1 August 2024}}</ref><ref name="PubChem-Norepinephrine">{{cite web | title=Norepinephrine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/439260 | access-date=1 August 2024}}</ref>

Isoprenaline is used pharmaceutically as the [[hydrochloride]] and [[sulfate]] [[salt (chemistry)|salt]]s.<ref name="IndexNominum2004" /> It is also used to a much lesser extent as the [[free base]].<ref name="IndexNominum2004" />

Isoprenaline is a [[racemic mixture]] of [[levorotatory]] and [[dextrorotatory]] [[enantiomer]]s.<ref name="PubChem" /><ref name="DrugBank" /><ref name="ChemSpider" /> The levorotatory or (''R'')-enantiomer of isoprenaline is known as levisoprenaline ({{Abbrlink|INN|International Nonproprietary Name}}) but was never marketed.<ref name="Elks2014" /><ref name="MortonHall2012" /><ref name="MortonHall2012-Levisoprenaline">{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA164 | access-date=2024-08-01 | page=164}}</ref>

Synthetic analogues closely related to isoprenaline include [[arbutamine]], [[dichloroisoprenaline]] (dichloroisoproterenol), [[hexoprenaline]], [[isoetharine]] (α-ethylisoprenaline), [[orciprenaline]] (metaproterenol; a [[positional isomer]] of isoprenaline), [[prenalterol]], and [[soterenol]] (3-methanesulfonamidylisoprenaline), among others.<ref name="Waldeck2002" />

==History==
Isoprenaline was discovered in 1940<ref name="Waldeck2002">{{cite journal | vauthors = Waldeck B | title = Beta-adrenoceptor agonists and asthma--100 years of development | journal = Eur J Pharmacol | volume = 445 | issue = 1-2 | pages = 1–12 | date = June 2002 | pmid = 12065188 | doi = 10.1016/s0014-2999(02)01728-4 | url = }}</ref> and was developed in the 1940s.<ref name="Morgan1990" /> It was first approved for medical use in 1947 in the [[United States]].<ref name="MozayaniRaymon2003">{{cite book| vauthors = Mozayani A, Raymon L |title=Handbook of Drug Interactions: A Clinical and Forensic Guide|date=2003|publisher=Springer Science & Business Media|isbn=978-1-59259-654-6|pages=541–542|url=https://books.google.com/books?id=dwMyBwAAQBAJ&pg=PA541|language=en}}</ref> Isoprenaline was one of the first [[synthetic compound|synthetic]] [[sympathomimetic]] [[amine]]s, was the first [[binding selectivity|selective]] [[beta-adrenergic agonist|β-adrenergic receptor agonist]], and was the first major sympathomimetic agent devoid of [[vasopressor|pressor]] effects.<ref name="Morgan1990">{{cite journal | vauthors = Morgan DJ | title = Clinical pharmacokinetics of beta-agonists | journal = Clin Pharmacokinet | volume = 18 | issue = 4 | pages = 270–294 | date = April 1990 | pmid = 1969785 | doi = 10.2165/00003088-199018040-00002 | url = }}</ref><ref name="RuženaJindraRenáta2020">{{cite journal | vauthors = Ružena Č, Jindra V, Renáta H | title=Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis | journal=Open Chemistry | volume=18 | issue=1 | date=18 June 2020 | issn=2391-5420 | doi=10.1515/chem-2020-0056 | pages=628–647| doi-access=free }}</ref>

Between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand there was an increase in deaths among people using isoprenaline to treat asthma. This was attributed to unintentional [[overdose]]: the inhalers produced in that area were dispensing five times the dosage dispensed by inhalers produced in the United States and Canada, where the deaths were not observed.<ref name="PearceHensley1998">{{cite journal | vauthors = Pearce N, Hensley MJ | title = Epidemiologic studies of beta agonists and asthma deaths | journal = Epidemiologic Reviews | volume = 20 | issue = 2 | pages = 173–186 | year = 1998 | pmid = 9919437 | doi = 10.1093/oxfordjournals.epirev.a017979 | doi-access = free }}</ref><ref name="Jalba2008">{{cite journal | vauthors = Jalba MS | title = Three generations of ongoing controversies concerning the use of short acting beta-agonist therapy in asthma: a review | journal = The Journal of Asthma | volume = 45 | issue = 1 | pages = 9–18 | date = 2008 | pmid = 18259990 | doi = 10.1080/02770900701495512 | s2cid = 31732029 }}</ref>

The short [[duration of action]] and poor [[oral administration|oral]] activity of isoprenaline led to the development of the much longer-acting and orally active [[orciprenaline]] (metaproterenol).<ref name="Derendorf1995">{{cite book | vauthors = Dserendorf H | title=Drug Actions: Basic Principles and Theraputic Aspects | publisher=CRC-Press | year=1995 | isbn=978-0-8493-7774-7 | url=https://books.google.com/books?id=IvN4mZxraMkC&pg=PA227 | access-date=1 August 2024 | page=227}}</ref><ref name="Morgan1990" />

==Society and culture==

===Names===
''Isoprenaline'' is the major [[generic term|generic name]] of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}, {{Abbrlink|BAN|British Approved Name}}, and {{Abbrlink|DCF|Dénomination Commune Française}}.<ref name="Elks2014">{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA710 | access-date=1 August 2024 | page=710}}</ref><ref name="IndexNominum2004">{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum: International Drug Directory | publisher=Medpharm Scientific Publishers | series=Index Nominum: International Drug Directory | year=2004 | isbn=978-3-88763-101-7 | url=https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA662 | access-date=1 August 2024 | page=662}}</ref><ref name="MortonHall2012">{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA157 | access-date=1 August 2024 | page=157}}</ref><ref name="Drugs.com">{{cite web | title=Isoprenaline | website=drugs.com | date=6 August 2017 | url=https://www.drugs.com/international/isoprenaline.html | archive-url=https://web.archive.org/web/20190626083242/https://www.drugs.com/international/isoprenaline.html | archive-date=26 June 2019 | url-status=dead | access-date=1 August 2024}}</ref> ''Isoprenalina'' is its [[Italian language|Italian]] generic name and its {{Abbrlink|DCIT|Denominazione Comune Italiana}}.<ref name="IndexNominum2004" /><ref name="Drugs.com" /> ''Isoprenaline hydrochloride'' and ''isoprenaline sulfate'' are its {{Abbrlink|BANM|British Approved Name}} in the case of the [[hydrochloride]] and [[sulfate]] [[salt (chemistry)|salt]]s, respectively.<ref name="IndexNominum2004" /> ''Isoproterenol'' is another important synonym of the drug.<ref name="Elks2014" /><ref name="IndexNominum2004" /><ref name="Drugs.com" /> ''Isoproterenol hydrochloride'' is its {{Abbrlink|USAN|United States Adopted Name}} and {{Abbrlink|JAN|Japanese Accepted Name}} in the case of the hydrochloride salt and ''isoproterenol sulfate'' is its {{Abbr|USAN|United States Adopted Name}} and {{Abbr|JAN|Japanese Accepted Name}} in the case of the sulfate salt.<ref name="Elks2014" /><ref name="IndexNominum2004" /><ref name="MortonHall2012" /><ref name="Drugs.com" /> Other synonyms of the drug include ''isopropylnorepinephrine'', ''isopropylnoradrenaline'', and ''isopropydine''.<ref name="Elks2014" /><ref name="IndexNominum2004" /><ref name="MortonHall2012" /><ref name="Drugs.com" /> It is additionally known by the former developmental code name ''WIN-5162''.<ref name="IndexNominum2004" /><ref name="Drugs.com" />

Isoprenaline has been marketed under many brand names worldwide.<ref name="IndexNominum2004" /><ref name="Drugs.com" /> These include Aleudrina, Asthpul, Iludrin, Iprenol, Isomenyl, Isuprel, Isoprenaline, Isoprenalina, Isoproterenol, Neo-Epinine, Neodrenal, Proternol, and Saventrine, among others.<ref name="IndexNominum2004" /><ref name="Drugs.com" /> It is also marketed as a [[combination drug]] with [[cromoglicic acid]] as Frenal Compositum, in combination with [[pronase]] as Isopal P, and in combination with [[atropine]] as Stmerin D.<ref name="Drugs.com" />

==References==
{{Reflist}}


{{Cardiac stimulants excluding cardiac glycosides}}
{{Drugs for obstructive airway diseases}}
{{Adrenergic receptor modulators}}
{{TAAR ligands}}
{{Phenethylamines}}

[[Category:Antiasthmatic drugs]]
[[Category:Alpha-adrenergic agonists]]<!-- At higher concentrations -->
[[Category:Beta1-adrenergic agonists]]
[[Category:Beta2-adrenergic agonists]]
[[Category:Bronchodilators]]
[[Category:Cardiac stimulants]]
[[Category:Catecholamines]]
[[Category:Chemical substances for emergency medicine]]
[[Category:Drugs acting on the cardiovascular system]]
[[Category:Inotropic agents]]
[[Category:Isopropylamino compounds]]
[[Category:Peripherally selective drugs]]
[[Category:Phenylethanolamines]]
[[Category:Sympathomimetic amines]]
[[Category:TAAR1 agonists]]
[[Category:Vasodilators]]