Isoprenaline was one of the firstsyntheticsympathomimeticamines and was the firstselective β-adrenergic receptor agonist.[7][14] The medication was discovered in 1940[5] and was introduced for medical use in 1947.[15]
Historically, it was used to treatasthma via metered aerosol or nebulizing devices; it was also available in sublingual, oral, intravenous, and intramuscular formulations.[15] The U.S. National Asthma Education and Prevention Program Expert Panel recommends against its use as a nebulizer for acute bronchoconstriction.[18]
Many formulations of isoprenaline appear to have been discontinued in theUnited States and many other countries.[4][1][2][3] In the United States, it remains available only as aninjectablesolution.[4] It was previously also available in the United States as a solution, meteredaerosol, powder, or disc forinhalation and as atablet forsublingual andrectal administration, but these formulations were discontinued.[4]
Isoprenaline isexcreted primarily in theurine, assulfateconjugates.[7][31][32][3] It is excreted 59 to 107% in urine and 12 to 27% infeces.[3] 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.[3][6]
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 unintentionaloverdose: 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.[38][39]
The shortduration of action and poororal activity of isoprenaline led to the development of the much longer-acting and orally activeorciprenaline (metaproterenol).[40][7]
Isoprenaline is the majorgeneric name of the drug and itsINNTooltip International Nonproprietary Name,BANTooltip British Approved Name, andDCFTooltip Dénomination Commune Française.[35][1][36][2]Isoprenalina is itsItalian generic name and itsDCITTooltip Denominazione Comune Italiana.[1][2]Isoprenaline hydrochloride andisoprenaline sulfate are itsBANMTooltip British Approved Name in the case of thehydrochloride andsulfatesalts, respectively.[1]Isoproterenol is another important synonym of the drug.[35][1][2]Isoproterenol hydrochloride is itsUSANTooltip United States Adopted Name andJANTooltip Japanese Accepted Name in the case of the hydrochloride salt andisoproterenol sulfate is itsUSAN andJAN in the case of the sulfate salt.[35][1][36][2] Other synonyms of the drug includeisopropylnorepinephrine,isopropylnoradrenaline, andisopropydine.[35][1][36][2] It is additionally known by the former developmental code nameWIN-5162.[1][2]
Isoprenaline has been marketed under many brand names worldwide.[1][2] These include Aleudrina, Asthpul, Iludrin, Iprenol, Isomenyl, Isuprel, Isoprenaline, Isoprenalina, Isoproterenol, Neo-Epinine, Neodrenal, Proternol, and Saventrine, among others.[1][2] It is also marketed as acombination drug withcromoglicic acid as Frenal Compositum, in combination withpronase as Isopal P, and in combination withatropine as Stmerin D.[2]
^Cohagan B, Brandis D (August 2022). "Torsade de Pointes".StatPearls. Treasure Island (FL): StatPearls Publishing.PMID29083738.NBK459388.
^Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, et al. (August 2019). "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".Circulation.140 (8):e382 –e482.doi:10.1161/CIR.0000000000000628.PMID30586772.
^abEmilien G, Maloteaux JM (February 1998). "Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists".Eur J Clin Pharmacol.53 (6):389–404.doi:10.1007/s002280050399.PMID9551698.
^abcdOlesen J, Hougård K, Hertz M (1978). "Isoproterenol and propranolol: ability to cross the blood-brain barrier and effects on cerebral circulation in man".Stroke.9 (4):344–349.doi:10.1161/01.str.9.4.344.PMID209581.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
^Crystal GJ, Salem MR (October 2002). "Beta-adrenergic stimulation restores oxygen extraction reserve during acute normovolemic hemodilution".Anesth Analg.95 (4):851–857, table of contents.doi:10.1097/00000539-200210000-00011.PMID12351256.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).
^Jalba MS (2008). "Three generations of ongoing controversies concerning the use of short acting beta-agonist therapy in asthma: a review".The Journal of Asthma.45 (1):9–18.doi:10.1080/02770900701495512.PMID18259990.S2CID31732029.
Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as theList of trace amines,TAAR, andTAAR1 pages.See also:Receptor/signaling modulators
