View source for Practolol

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464212885
| IUPAC_name = (''RS'')-''N''-<nowiki/>{4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl}acetamide
| image = Practolol structure.svg
| width = 250
<!--Clinical data-->
| tradename =
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 6673-35-4
| ATC_prefix = C07
| ATC_suffix = AB01
| PubChem = 4883
| IUPHAR_ligand = 555
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01297
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4715
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = SUG9176GRW
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D05587
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 258351
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 6995
<!--Chemical data-->
| C=14 | H=22 | N=2 | O=3
| smiles = O=C(Nc1ccc(OCC(O)CNC(C)C)cc1)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DURULFYMVIFBIR-UHFFFAOYSA-N
}}

'''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.<ref>{{cite journal | vauthors = Wright P | title = Untoward effects associated with practolol administration: oculomucocutaneous syndrome | journal = British Medical Journal | volume = 1 | issue = 5958 | pages = 595–598 | date = March 1975 | pmid = 1125623 | pmc = 1672788 | doi = 10.1136/bmj.1.5958.595 }}</ref>

==History==
The compound was studied by scientists at the Research Department of the [[Imperial Chemical Industries|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.<ref>{{cite journal | vauthors = Barrett AM, Carter J, Fitzgerald JD, Hull R, Le Count D | title = A new type of cardioselective adrenoceptive blocking drug | journal = British Journal of Pharmacology | volume = 48 | issue = 2 | pages = 340P | date = June 1973 | pmid = 4147428 | pmc = 1776195 | doi = 10.1111/j.1476-5381.1973.tb06921.x }}</ref><ref>{{cite journal | vauthors = Dunlop D, Shanks RG | title = Selective blockade of adrenoceptive beta receptors in the heart | journal = British Journal of Pharmacology and Chemotherapy | volume = 32 | issue = 1 | pages = 201–218 | date = January 1968 | pmid = 4384337 | pmc = 1570292 | doi = 10.1111/j.1476-5381.1968.tb00444.x }}</ref>

==Side effects==
Side effects are similar to those of other [[beta blocker]]s, such as bronchoconstriction, cardiac failure, cold extremities, fatigue and depression, hypoglycaemia.<ref name=Rang&Dale6th>{{cite book | vauthors = Flower R, Rang HP, Dale MM, Ritter JM |title=Rang & Dale's pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2007 |isbn=978-0-443-06911-6 }}</ref>

Furthermore, chronic use of practolol may cause [[oculomucocutaneous syndrome]],<ref name=Rang&Dale6th/> a severe syndrome whose signs include conjunctivitis [[Dryness (medical)|sicca]] and [[psoriasiform rash]]es, [[otitis]] and [[sclerosing serositis]]. This syndrome has not been observed with other such beta blockers.<ref>{{cite web | url = http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20%28General%20Monographs-%20C%29/CORGARD.html | work = rxmed.com | title = Nadolol | access-date = 1 July 2010 }}</ref>

==Ban==
This drug has been withdrawn from the market in India.<ref name="ban">{{cite web|url = http://cdsco.nic.in/html/drugsbanned.html|title = Drugs banned in India|publisher = Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India|access-date = 2013-09-17|archive-url = https://web.archive.org/web/20150221053621/http://cdsco.nic.in/html/drugsbanned.html|url-status = |archive-date=2015-02-21 }}</ref>

==Synthesis==
The part of the structure coming from ('''1''') is based on [[paracetamol]].
[[File:Practolol synthesis.svg|thumb|center|600px|Practolol synthesis:<ref>{{cite journal | vauthors = Danilewicz JC, Kemp JE | title = Absolute configuration by asymmetric synthesis of (+)-1-(4-acetamidophenoxy)-3-(isopropylamino)-propan-z-ol (practolol) | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 2 | pages = 168–169 | date = February 1973 | pmid = 4405110 | doi = 10.1021/jm00260a020 }}</ref> Howe, Smith, {{Cite patent|country=NL|number=6512676}}; eidem, {{US patent|3408387}} (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|date= February 2018}}

== References ==
{{reflist}}

== External links ==
;Scientific information / studies
* [http://jpet.aspetjournals.org/cgi/content/abstract/195/1/133 Guinea Pig study from 1975]
* [http://jpet.aspetjournals.org/cgi/content/abstract/219/1/207 Liver effect study from 1981]
* [https://web.archive.org/web/20070310210639/http://bja.oxfordjournals.org/cgi/content/abstract/52/1/91 Study of uses during surgery]
* [https://web.archive.org/web/20060311084045/http://www.registech.com/chiral/applications/practolol.htm Molecular structure]
;General information
* {{DiseasesDB|10479}}

{{Beta blockers}}
{{Adrenergics}}

[[Category:Beta blockers]]
[[Category:Acetanilides]]
[[Category:N-isopropyl-phenoxypropanolamines]]
[[Category:Hepatotoxins]]
[[Category:Withdrawn drugs]]
[[Category:Isopropylamino compounds]]