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 Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

. 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.

History

The compound was studied by scientists at the Research Department of the ICI Pharmaceuticals Division in

Alderley Park Alderley Park was a country estate at Nether Alderley, Cheshire, England, between Macclesfield and Knutsford. It was the residence of the Stanley family of Alderley from the 1500s. It became the headquarters of ICI Pharmaceuticals in the 1950s. I ...

with physiologists at the

University of Leeds , mottoeng = And knowledge will be increased , established = 1831 – Leeds School of Medicine1874 – Yorkshire College of Science1884 - Yorkshire College1887 – affiliated to the federal Victoria University1904 – 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.

Side effects

Side effects are similar to those of other beta blockers, such as bronchoconstriction, cardiac failure, cold extremities, fatigue and depression, hypoglycaemia. Furthermore, chronic use of practolol may cause oculomucocutaneous syndrome, a severe syndrome whose signs include conjunctivitis sicca and psoriasiform rashes,

otitis Otitis is a general term for inflammation or infection, inner ear infection, middle ear infection of the ear, in both humans and other animals. When infection is present, it may be viral or bacterial. When inflammation is present due to fluid buil ...

and sclerosing serositis. This syndrome has not been observed with other such beta blockers.

Ban

This drug has been withdrawn from the market in India.

Synthesis

The part of the structure coming from (1) is based on

paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...

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 4-Toluenesulfonyl chloride (''p''-toluenesulfonyl chloride, toluene-''p''-sulfonyl chloride) is an organic compound with the formula CH3C6H4SO2Cl. This white, malodorous solid is a reagent widely used in organic synthesis. Abbreviated TsCl or To ...

and pyridine, then treated with NaOH in dimethylsulfoxide to yield 3. Epoxide opening with

isopropylamine Isopropylamine (monoisopropyl amine, MIPA, 2-Propylamine) is an organic compound, an amine. It is a hygroscopic colorless liquid with ammonia-like odor. It is miscible with water and flammable. It is a valuable intermediate in chemical industry. ...

leads to optically active prolactolol (4).

References

External links

;Scientific information / studies
Guinea Pig study from 1975

Liver effect study from 1981

Study of uses during surgery

;General information * Beta blockers Acetanilides N-isopropyl-phenoxypropanolamines Hepatotoxins Withdrawn drugs Isopropyl compounds {{antihypertensive-stub