Practolol

Practolol
Clinical data

ATC code	C07AB01 (WHO)
Identifiers
IUPAC name (RS)-N-{4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl}acetamide
CAS Number	6673-35-4^Y
PubChem (CID)	4883
IUPHAR/BPS	555
DrugBank	DB01297^Y
ChemSpider	4715^Y
UNII	SUG9176GRW^Y
KEGG	D05587^N
ChEBI	CHEBI:258351^Y
ChEMBL	CHEMBL6995^Y
ECHA InfoCard	100.027.012
Chemical and physical data
Formula	C₁₄H₂₂N₂O₃
Molar mass	266.336 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(Nc1ccc(OCC(O)CNC(C)C)cc1)C
InChI 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)^Y Key:DURULFYMVIFBIR-UHFFFAOYSA-N^Y
^NY (what is this?) (verify)

Practolol (Eraldin, Dalzic, Praktol, Cardiol, Pralon, Cordialina, Eraldina, Teranol) is a selective beta 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. (British Medical Journal, March 15, 1975)

History

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.^[1] ^[2]

Side effects

Side effects are similar to those of other beta blockers, such as bronchoconstriction, cardiac failure, cold extremities, fatigue and depression, hypoglycaemia.^[3]

Furthermore, chronic use of practolol may cause oculomucocutaneous syndrome,^[3] 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.^[4]

Ban

This drug has been withdrawn from the market in India.^[5]

Synthesis

NB: Obviously, part of the structure is based on paracetamol.

Practolol synthesis:^[6] 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) 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).

References

↑ BARRETT, A.M.; et al. (June 1973). "A new type of cardioselective adrenoceptive blocking drug". Br J Pharmacol. 48 (2): 340P. PMC 1776195. PMID 4147428.
↑ DUNLOP, D.; et al. (January 1968). "SELECTIVE BLOCKADE OF ADRENOCEPTIVE BETA RECEPTORS IN THE HEART drug" (PDF). Br. J. Pharmac. Chemother. 32 (1): 201–218. doi:10.1111/j.1476-5381.1968.tb00444.x. PMC 1570292. PMID 4384337. Retrieved 15 June 2015.
1 2 Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-06911-5.
↑ rxmed.com > Nadolol Retrieved on 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, J. C.; Kemp, J. E. G. (1973). "Absolute configuration by asymmetric synthesis of (+)-1-(4-acetamidophenoxy)-3-(isopropylamino)propan-2-ol) (practolol)". Journal of Medicinal Chemistry. 16 (2): 168. doi:10.1021/jm00260a020. PMID 4405110.

External links

Scientific information / studies

General information

DDB 10479

Beta blockers (C07)

β, non-selective	Alprenolol Bopindolol Bupranolol Carteolol Cloranolol Mepindolol Nadolol Oxprenolol Penbutolol Pindolol/Iodopindolol Propranolol Sotalol Tertatolol Timolol

β₁-selective	Acebutolol Atenolol Betaxolol Bevantolol Bisoprolol Celiprolol Epanolol Esmolol Landiolol Metoprolol Nebivolol Practolol S-Atenolol Talinolol

β₂-selective	Butaxamine

α₁- + β-selective	Arotinolol Carvedilol Labetalol

^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

Adrenergic receptor modulators

α₁

Agonists 6-FNE Amidephrine Anisodine Buspirone Cirazoline Corbadrine Dexisometheptene Dipivefrine Dopamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etilefrine Etilevodopa Ethylnorepinephrine Indanidine Isometheptene L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Melevodopa Metaraminol Methoxamine Methyldopa Midodrine Naphazoline Norepinephrine Octopamine (drug) Oxymetazoline Phenylephrine Phenylpropanolamine Pseudoephedrine Synephrine Tetryzoline Tiamenidine XP21279 Xylometazoline

Antagonists Abanoquil Adimolol Ajmalicine Alfuzosin Amosulalol Anisodamine Arotinolol Atiprosin Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone) Benoxathian Buflomedil Bunazosin Carvedilol Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., ergotamine, dihydroergotamine, lisuride, terguride) Etoperidone Eugenodilol Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 Labetalol mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Nefazodone Neldazosin Niaprazine Nicergoline Niguldipine Pardoprunox Pelanserin Phendioxan Phenoxybenzamine Phentolamine Piperoxan Prazosin Quinazosin Ritanserin Silodosin Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Trazodone Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, imipramine, trimipramine) Trimazosin Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Urapidil WB-4101 Zolertine

α₂

Agonists (R)-3-Nitrobiphenyline 4-NEMD 6-FNE Amitraz Apraclonidine Brimonidine Cannabivarin Clonidine Corbadrine Detomidine Dexmedetomidine Dihydroergotamine Dipivefrine Dopamine Droxidopa (L-DOPS) Etilevodopa Ephedrine Ergotamine Epinephrine Etilefrine Ethylnorepinephrine Guanabenz Guanfacine Guanoxabenz L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Lofexidine Medetomidine Melevodopa Methyldopa Mivazerol Naphazoline Norepinephrine Oxymetazoline Phenylpropanolamine Piperoxan Pseudoephedrine Rilmenidine Romifidine Talipexole Tetrahydrozoline Tiamenidine Tizanidine Tolonidine Urapidil XP21279 Xylazine Xylometazoline

Antagonists 1-PP Adimolol Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine, clozapine, lurasidone, paliperidone, quetiapine, risperidone, zotepine) Azapirones (e.g., buspirone, tandospirone) BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan mCPP Mianserin Mirtazapine NAN-190 Olanzapine Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine SB-269970 Setiptiline Spiroxatrine Sunepitron Tolazoline Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Yohimbine

Agonists Abediterol Alifedrine Amibegron Arbutamine Arformoterol Arotinolol BAAM Bambuterol Befunolol Bitolterol Broxaterol Buphenine Carbuterol Carmoterol Cimaterol Clenbuterol Corbadrine Denopamine Dipivefrine Dobutamine Dopamine Dopexamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etafedrine Etilefrine Etilevodopa Ethylnorepinephrine Fenoterol Formoterol Hexoprenaline Higenamine Indacaterol Isoetarine Isoprenaline Isoxsuprine L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Levosalbutamol Mabuterol Melevodopa Methoxyphenamine Methyldopa Mirabegron Norepinephrine Orciprenaline Oxyfedrine PF-610355 Phenylpropanolamine Pirbuterol Prenalterol Ractopamine Procaterol Pseudoephedrine Reproterol Rimiterol Ritodrine Salbutamol Salmeterol Solabegron Terbutaline Tretoquinol Tulobuterol Vilanterol Xamoterol XP21279 Zilpaterol Zinterol

Antagonists Acebutolol Adaprolol Adimolol Afurolol Alprenolol Alprenoxime Amosulalol Ancarolol Arnolol Arotinolol Atenolol Befunolol Betaxolol Bevantolol Bisoprolol Bopindolol Bornaprolol Brefonalol Bucindolol Bucumolol Bufetolol Bufuralol Bunitrolol Bunolol Bupranolol Butaxamine Butidrine Butofilolol Capsinolol Carazolol Carpindolol Carteolol Carvedilol Celiprolol Cetamolol Cicloprolol Cinamolol Cloranolol Cyanopindolol Dalbraminol Dexpropranolol Diacetolol Dichloroisoprenaline Dihydroalprenolol Dilevalol Diprafenone Draquinolol Ecastolol Epanolol Ericolol Ersentilide Esatenolol Esprolol Eugenodilol Exaprolol Falintolol Flestolol Flusoxolol Hydroxycarteolol Hydroxytertatolol ICI-118,551 Idropranolol Indenolol Indopanolol Iodocyanopindolol Iprocrolol Isoxaprolol Isamoltane Labetalol Landiolol Levobetaxolol Levobunolol Levomoprolol Medroxalol Mepindolol Metipranolol Metoprolol Moprolol Nadolol Nadoxolol Nebivolol Nifenalol Nipradilol Oxprenolol Pacrinolol Pafenolol Pamatolol Pargolol Penbutolol Pindolol Practolol Primidolol Procinolol Pronethalol Propafenone Propranolol Ridazolol Ronactolol Soquinolol Sotalol Spirendolol SR 59230A Sulfinalol Talinolol Tazolol Tertatolol Tienoxolol Tilisolol Timolol Tiprenolol Tolamolol Toliprolol Xibenolol Xipranolol

See also: Dopaminergics

Melatonergics

Serotonergics

Monoamine reuptake and release modulators

Monoamine metabolism modulators

Monoamine neurotoxins

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