6452-73-9

Oxprenolol is an orally bioavailable β-adrenergic receptor (β-AR) antagonist (K_i = 7.10 nM in a radioligand binding assay using rat heart tissue). It is non-selective and binds to both β₁- and β₂-ARs (K_ds = 2.09 and 1.35 nM in isolated rat heart and uterus, respectively). Oxprenolol is selective for β-ARs over serotonin (5-HT) receptors in rat sarcolemmal membrane preparations (IC₅₀s = 4.13 and 23,300 nM, respectively), but it binds to 5-HT_1A receptors in rat hippocampus and 5-HT_1B in rat striatum (K_is = 94.2 and 642 nM, respectively). Formulations containing oxprenolol have been used to treat hypertension and angina pectoris.

White Solid

Trasicor,Ciba Geigy ,Italy,1970

Antihypertensive;Adrenergic receptor antagonist

β-Adrenergic blocker. Antihypertensive, antianginal, antiarrhythmic.

75 grams of pyrocatechol monoallyl ether, 75 grams of epichlorohydrin, 75 grams of potassium carbonate and 400 ml of acetone are stirred and heated at the boil for 12 hours. The potassium carbonate is then filtered off. The solvent is distilled off in a water-jet vacuum. The residual oil is dissolved in ether and agitated with 2 N sodium hydroxide solution. The ether is separated, dried and distilled off. The residue is distilled in a water-jet vacuum. 3-(ortho-allyloxy-phenoxy)-1,2-epoxypropane passes over at 145° to 157°C under 11 mm Hg pressure. A solution of 15 grams of 3-(ortho-allyloxyphenoxy)-1,2-epoxypropane and 15 grams of isopropylamine in 20 ml of ethanol is refluxed for 4 hours. The excess amine and the alcohol are then distilled off under vacuum, to leave 1-isopropylamino-2-hydroxy-3-(orthoallyloxy-phenoxy)-propane which melts at 75° to 80°C after recrystallization from hexane.

Trasicor (Novartis).

Antiarrhythmic

Non-selective β -adrenergic antagonist.

Beta-1 adrenoceptor blocker:
Hypertension
Angina
Arrhythmias
Anxiety

Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: NSAIDs antagonise hypotensive effect.
Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide.
Antidepressants: enhanced hypotensive effect with MAOIs.
Antihypertensives: enhanced hypotensive effect; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin; increased risk of withdrawal hypertension with clonidine; increased risk of bradycardia and AV block with diltiazem; severe hypotension and heart failure occasionally with nifedipine; asystole, severe hypotension and heart failure with verapamil.
Antimalarials: increased risk of bradycardia with mefloquine.
Antipsychotics: enhanced hypotensive effect with phenothiazines.
Cytotoxics: possible increased risk of bradycardia with crizotinib.
Diuretics: enhanced hypotensive effect.
Fingolimod: possibly increased risk of bradycardia.
Moxisylyte: possibly severe postural hypotension.
Sympathomimetics: severe hypertension with adrenaline and noradrenaline (especially with nonselective beta-blockers) and possibly with dopamine.

Oxprenolol is extensively metabolised in the liver, direct O-glucuronidation being the major metabolic pathway and oxidative reactions minor ones. Oxprenolol is excreted chiefly in the urine (almost exclusively in the form of inactive metabolites).

Store at -20°C

[1] TAKAFUMI NAGATOMO . BINDING CHARACTERISTICS OF 3H-DIHYDROALPRENOLOL TO β-ADRENOCEPTORS OF RAT HEART TREATED WITH NEURAMINIDASE[J]. Japanese journal of pharmacology, 1983, 33 4: Pages 851-857. DOI: 10.1016/s0021-5198(19)52475-1
[2] ABRAHAMSSON T. The β1- and β2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol: a study in the isolated right atrium and uterus of the rat[J]. British Journal of Pharmacology, 1986, 87 4: 657-664. DOI: 10.1111/j.1476-5381.1986.tb14582.x
[3] I. MORETTI-ROJAS. Serotonergic and adrenergic regulation of skeletal muscle metabolism in the rat. II. The use of [125I]iodolysergic acid diethylamide and [125I]iodopindolol as probes of sarcolemmal receptor function and specificity.[J]. The Journal of Biological Chemistry, 1983, 30 1: 12499-12508. DOI: 10.1016/s0021-9258(17)44204-9
[4] MICHEL LANGLOIS. Structural analysis by the comparative molecular field analysis method of the affinity of β-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptors[J]. European Journal of Pharmacology: Molecular Pharmacology, 1993, 244 1: Pages 77-87. DOI: 10.1016/0922-4106(93)90061-d
[5] M. RUSSO J C. Oxprenolol Hydrochloride: Pharmacology, Pharmacokinetics, Adverse Effects and Clinical Efficacy[J]. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 1983, 2010 1. DOI: 10.1002/j.1875-9114.1983.tb03224.x