Practolol (Eraldin, Dalzic, Praktol, Cardiol, Pralon, Cordialina, Eraldina, Teranol) is a selective beta blocker (beta-1 blocker) that has been used in the emergency treatment of cardiac arrhythmias. Practolol is no longer used as it is highly toxic despite the similarity of its chemical formula to propranolol. After its introduction, keratoconjunctivitis sicca, conjunctival scarring, fibrosis, metaplasia, and shrinkage developed in 27 patients as an adverse reaction to practolol. Rashes, nasal and mucosal ulceration, fibrous or plastic peritonitis, pleurisy, cochlear damage, and secretory otitis media also occurred in some cases. Three patients suffered profound visual loss though most retained good vision. Symptoms and signs improved on withdrawal of the drug, but reduction of tear secretion persisted in most patients.[1]
The compound was studied by scientists at the Research Department of the ICI Pharmaceuticals Division in Alderley Park with physiologists at the University of Leeds in the early 1970s when it was known as compound ICI 66082; they utilised dogs, cats and rats in their investigations. Earlier research had also been carried out as early as 1967 on this and similar molecules by other research teams also with ICI.[2][3]
Side effectsedit
Side effects are similar to those of other beta blockers, such as bronchoconstriction, cardiac failure, cold extremities, fatigue and depression, hypoglycaemia.[4]
Furthermore, chronic use of practolol may cause oculomucocutaneous syndrome,[4] a severe syndrome whose signs include conjunctivitis sicca and psoriasiform rashes, otitis and sclerosing serositis. This syndrome has not been observed with other such beta blockers.[5]
Banedit
This drug has been withdrawn from the market in India.[6]
Synthesisedit
The part of the structure coming from (1) is based on paracetamol.
Practolol synthesis:[7] Howe, Smith, NL 6512676; eidem, U.S. patent 3,408,387 (1966, 1968, to I.C.I.).
A synthesis is available which relates the absolute configuration of the more potent optical isomer to (+)-lactic acid. The glycerol derivative (2) is available from D-mannitol and retains optical activity as the two 1° alcohol functions are differentially protected. Displacement with sodium p-acetamidophenoxide (1, deprotonated paracetamol) gives 3 which is deprotected with dilute acid, the primary alcohol function is selectively reacted with one molar equivalent of tosyl chloride and pyridine, then treated with NaOH in dimethylsulfoxide to yield 3. Epoxide opening with isopropylamine leads to optically active prolactolol (4).[citation needed]
Referencesedit
^Wright P (March 1975). "Untoward effects associated with practolol administration: oculomucocutaneous syndrome". British Medical Journal. 1 (5958): 595–598. doi:10.1136/bmj.1.5958.595. PMC1672788. PMID 1125623.
^Barrett AM, Carter J, Fitzgerald JD, Hull R, Le Count D (June 1973). "A new type of cardioselective adrenoceptive blocking drug". British Journal of Pharmacology. 48 (2): 340P. doi:10.1111/j.1476-5381.1973.tb06921.x. PMC1776195. PMID 4147428.
^Dunlop D, Shanks RG (January 1968). "Selective blockade of adrenoceptive beta receptors in the heart". British Journal of Pharmacology and Chemotherapy. 32 (1): 201–218. doi:10.1111/j.1476-5381.1968.tb00444.x. PMC1570292. PMID 4384337.
^ abFlower R, Rang HP, Dale MM, Ritter JM (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN978-0-443-06911-6.
^. Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India. Archived from the original on 2015-02-21. Retrieved 2013-09-17.
^Danilewicz JC, Kemp JE (February 1973). "Absolute configuration by asymmetric synthesis of (+)-1-(4-acetamidophenoxy)-3-(isopropylamino)-propan-z-ol (practolol)". Journal of Medicinal Chemistry. 16 (2): 168–169. doi:10.1021/jm00260a020. PMID 4405110.
practolol, eraldin, dalzic, praktol, cardiol, pralon, cordialina, eraldina, teranol, selective, beta, blocker, beta, blocker, that, been, used, emergency, treatment, cardiac, arrhythmias, longer, used, highly, toxic, despite, similarity, chemical, formula, pro. Practolol Eraldin Dalzic Praktol Cardiol Pralon Cordialina Eraldina Teranol is a selective beta blocker beta 1 blocker that has been used in the emergency treatment of cardiac arrhythmias Practolol is no longer used as it is highly toxic despite the similarity of its chemical formula to propranolol After its introduction keratoconjunctivitis sicca conjunctival scarring fibrosis metaplasia and shrinkage developed in 27 patients as an adverse reaction to practolol Rashes nasal and mucosal ulceration fibrous or plastic peritonitis pleurisy cochlear damage and secretory otitis media also occurred in some cases Three patients suffered profound visual loss though most retained good vision Symptoms and signs improved on withdrawal of the drug but reduction of tear secretion persisted in most patients 1 PractololClinical dataATC codeC07AB01 WHO IdentifiersIUPAC name RS N 4 2 hydroxy 3 isopropylamino propoxy phenyl acetamideCAS Number6673 35 4 YPubChem CID4883IUPHAR BPS555DrugBankDB01297 YChemSpider4715 YUNIISUG9176GRWKEGGD05587 NChEBICHEBI 258351 YChEMBLChEMBL6995 YCompTox Dashboard EPA DTXSID0021179ECHA InfoCard100 027 012Chemical and physical dataFormulaC 14H 22N 2O 3Molar mass266 341 g mol 13D model JSmol Interactive imageSMILES O C Nc1ccc OCC O CNC C C cc1 CInChI InChI 1S C14H22N2O3 c1 10 2 15 8 13 18 9 19 14 6 4 12 5 7 14 16 11 3 17 h4 7 10 13 15 18H 8 9H2 1 3H3 H 16 17 YKey DURULFYMVIFBIR UHFFFAOYSA N Y N Y what is this verify Contents 1 History 2 Side effects 3 Ban 4 Synthesis 5 References 6 External linksHistory editThe compound was studied by scientists at the Research Department of the ICI Pharmaceuticals Division in Alderley Park with physiologists at the University of Leeds in the early 1970s when it was known as compound ICI 66082 they utilised dogs cats and rats in their investigations Earlier research had also been carried out as early as 1967 on this and similar molecules by other research teams also with ICI 2 3 Side effects editSide effects are similar to those of other beta blockers such as bronchoconstriction cardiac failure cold extremities fatigue and depression hypoglycaemia 4 Furthermore chronic use of practolol may cause oculomucocutaneous syndrome 4 a severe syndrome whose signs include conjunctivitis sicca and psoriasiform rashes otitis and sclerosing serositis This syndrome has not been observed with other such beta blockers 5 Ban editThis drug has been withdrawn from the market in India 6 Synthesis editThe part of the structure coming from 1 is based on paracetamol nbsp Practolol synthesis 7 Howe Smith NL 6512676 eidem U S patent 3 408 387 1966 1968 to I C I A synthesis is available which relates the absolute configuration of the more potent optical isomer to lactic acid The glycerol derivative 2 is available from D mannitol and retains optical activity as the two 1 alcohol functions are differentially protected Displacement with sodium p acetamidophenoxide 1 deprotonated paracetamol gives 3 which is deprotected with dilute acid the primary alcohol function is selectively reacted with one molar equivalent of tosyl chloride and pyridine then treated with NaOH in dimethylsulfoxide to yield 3 Epoxide opening with isopropylamine leads to optically active prolactolol 4 citation needed References edit Wright P March 1975 Untoward effects associated with practolol administration oculomucocutaneous syndrome British Medical Journal 1 5958 595 598 doi 10 1136 bmj 1 5958 595 PMC 1672788 PMID 1125623 Barrett AM Carter J Fitzgerald JD Hull R Le Count D June 1973 A new type of cardioselective adrenoceptive blocking drug British Journal of Pharmacology 48 2 340P doi 10 1111 j 1476 5381 1973 tb06921 x PMC 1776195 PMID 4147428 Dunlop D Shanks RG January 1968 Selective blockade of adrenoceptive beta receptors in the heart British Journal of Pharmacology and Chemotherapy 32 1 201 218 doi 10 1111 j 1476 5381 1968 tb00444 x PMC 1570292 PMID 4384337 a b Flower R Rang HP Dale MM Ritter JM 2007 Rang amp Dale s pharmacology Edinburgh Churchill Livingstone ISBN 978 0 443 06911 6 Nadolol rxmed com Retrieved 1 July 2010 Drugs banned in India Central Drugs Standard Control Organization Dte GHS Ministry of Health and Family Welfare Government of India Archived from the original on 2015 02 21 Retrieved 2013 09 17 Danilewicz JC Kemp JE February 1973 Absolute configuration by asymmetric synthesis of 1 4 acetamidophenoxy 3 isopropylamino propan z ol practolol Journal of Medicinal Chemistry 16 2 168 169 doi 10 1021 jm00260a020 PMID 4405110 External links editScientific information studiesGuinea Pig study from 1975 Liver effect study from 1981 Study of uses during surgery Molecular structureGeneral informationDiseases Database DDB 10479 nbsp This antihypertensive related article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Practolol amp oldid 1160755381, wikipedia, wiki, book, books, library,
