| Description | Isoproterenol is a representative of the sympathomimetic drugs with high selectivity to β-adrenoreceptors. As was already noted, the addition to compounds of a bulky iso-propyl ortert-butyl group at the nitrogen atom of the β-phenylethylamino skeleton is associated withhigher affinity to β-adrenergic receptive regions than to α-adrenergic. Isoproterenol isdevoid of significant α-adrenergic agonistic action. Activation of β1-adrenergic receptorsin the heart increases positive chronotropic and ionotropic action. Peripheral vascularresistance is increased by the widening of blood vessels, primarily in skeletal muscle, butalso in renal and mesenteric blood circulation, which is caused by the β2-adrenergicsystem. |
| Chemical Properties | Folded color crystals. Melting point 155.5°C. Its hydrochloride and sulfate salts are usually used. They are white crystalline powder, soluble in water, insoluble in chloroform or ether. Odorless, slightly bitter taste. Its hydrochloride, [51-30-9], melting point 170-170 ° C (decomposition); base sulfate, [6700-39-6], melting point 128 ° C ° C (decomposition). |
| Originator | Isonorin,Smith, Miller and Patch,US,1949 |
| Uses | Isoproterenol is used in bronchospasms, asthma, cardiac block, and shock. |
| Uses | Isoprenaline is a potent β-agonist primarily acting at the β1-receptor. It ismainly used for the temporary emergency treatment of bradyarrhythmias. β2effects lead to broncho- and vasodilatation, with a decrease in SVR.Isoprenaline is only available in the UK via specialist importing companies.It is administered by i.v. infusion at a dose range of 0.5–20 μg min–1. |
| Uses | Bronchodilator. |
| Definition | ChEBI: A secondary amino compound that is noradrenaline in which one of the hydrogens attached to the nitrogen is replaced by an isopropyl group. A sympathomimetic acting almost exclusively on beta-adrenergic receptors, it is used (mainly as the hyrochloride salt) as a bronghodilator and heart stimulant for the management of a variety of cardiac disorders. |
| Indications | Isoproterenol is administered almost exclusively byinhalation from metered-dose inhalers or from nebulizers.The response to inhaled isoproterenol and other inhaledadrenomimetics is instantaneous. The action ofisoproterenol is short-lived, although an objectivemeasurement of pulmonary function has shown an effectiveduration of up to 3 hours. When it is administeredby inhalation, the cardiac effects of isoproterenolare relatively mild, although in some cases a substantialincrease in heart rate occurs. |
| Manufacturing Process | As described in US Patent 2,308,232, 100 g 3,4-dihydroxy-ω-chloroacetophenone, 200 cc ethyl alcohol and 200 cc of about 50% aqueousisopropylamine solution are boiled during 3 hours on the water bath with theuse of a reflux condenser, whereupon neutralizing with diluted sulfuric acid iscarried out and the sulfate, obtained upon cooling, from alcohol of 50% isrecrystallized; its MP is 245°C.
21 g 3,4-dihydroxy-ω-isopropylaminoacetophenone sulfate are hydrogenatedwith 50 cc methyl alcohol and 50 cc water, 0.5 g carbon and 3 cc palladiumchloride solution of 2%. After 2 hours the hydrogen absorption comes to astandstill, after the theoretical quantity of hydrogen has been absorbed. Afterconcentrating, the isopropylaminomethyl-(3,4-dihydroxyphenyl)carbinolsulfatecrystallizes out. It has a MP of 180°C after refining. |
| Brand name | Medihaler-ISO (3M Pharmaceuticals);Aerolone;Aerotrol;Afdosa;Aldo asma;Aleudrina;Anthastmin;Asmadren;Asmastop;Atom-asma;Dey-dose;Dispos-a-med;Duo-autohaler;Duo-medihaler;Dyspnoesan;Erydin;Frenal composium;Imuprel;Ingelan;Intal compositum;Iso-autohaler;Isonorin;Isoprel-neomistometer;Isoprop;Isorenin;Katwilon n;Lenoprel;Luf-iso;Medihaler-duo;Meterdos-iso;Neo epinine;Nephenalin;Norisodrin aerotol;Norisodrin with calcium idodide;Norosodrine;Older;Orotenol;Prenomiser;Propynalin;Protenol;Sedantosol;Sooner. |
| Therapeutic Function | Bronchodilator |
| World Health Organization (WHO) | Isoprenaline, a beta-adrenoreceptor agonist, was introduced in1949 as treatment for a number of cardiac disorders and as a bronchial dilator forthe symptomatic treatment of asthma. There is evidence that regular inhalation ofbronchodilator drugs is associated, in some cases with exacerbation of thedisease and with increased fatality rates. The underlying causes are disputed, butan increasing body of opinion now advocates regular maintenance therapy withinhaled, corticosteroids coupled with supplementary use as required of bronchialdrugs to suppress exacerbations. |
| General Description | Isoproterenol is a nonselective and prototypical -agonist ( β2/ β1=1). After oral administration,the absorption of ISO is rather erratic and undependable.The principal reason for its poor absorption characteristicsand relatively short DOA is its facile metabolism by sulfateand glucuronide conjugation of the phenolic OH groupsand O-methylation by COMT. Because it is a catechol, it issensitive to light and air. Aqueous solutions become pinkon standing. Unlike E and NE, ISO does not appear to undergo oxidative deamination by MAO. The drug hasDOA of 1 to 3 hours after inhalation. |
| Clinical Use | The cardiac stimulation caused by its 1-activity andits lack of oral activity have led to its diminished use infavor of more selective -agonists. The problems have beenovercome at least partially by the design and developmentof several noncatechol selective 2-agonists. These agentsrelax smooth muscle of the bronchi, uterus, and skeletalmuscle vascular supply. They find their primary use as bronchodilatorsin the treatment of acute and chronic bronchialasthma and other obstructive pulmonary diseases. |
| Clinical Use | Isoproterenol is used principally by inhalation forthe management of bronchospasm. It is also used intravenouslyfor asthma and as a stimulant in cardiac arrest. |
| Safety Profile | Poison by ingestion, subcutaneous, intravenous, and intraperitoneal routes. An experimental teratogen. Other experimental reproductive effects. Human systemic effects by intramuscular route: increased pulse and cardac rate. A bronchodilator. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx |
| Synthesis | Isoproterenol, 1-(3,4-dihydroxyphenyl)-2-iso-propylaminoethanol (11.1.8),is synthesized by an analogous scheme of making epinephrine. Interaction of |?-chloro-3,4-dihydroxyacetophenone (chloroacetylpyrocatechol) with isopropylamine gives |?-isopropylamino-3,4-dihydroxyacetophenone (11.1.7), reduction of the carbonyl group of which byhydrogen using a palladium on carbon catalyst gives isoproterenol (11.1.8) [11,12]. |
