Penbutolol

Absorption

>90%.

Toxicity

Symptoms of overdose include drowsiness, vertigo, headache, and atriventricular block.

Originator

Betapressin, Hoechst , W. Germany ,1980

The Uses of Penbutolol

Anti-adrenergic (β-receptor).

Background

Penbutolol is a drug in the beta-blocker class used to treat hypertension. Penbutolol binds both beta-1 and beta-2 adrenergic receptors, rendering it a non-selective beta-blocker. Penbutolol can act as a partial agonist at beta adrenergic receptors, since it is a sympathomimetric drug. Penbutolol also demonstrates high binding affinity to the 5-hydroxytryptamine receptor 1A with antagonistic effects. This binding characteristic of penbutolol is being investigated for its implications in Antidepressant Therapy. Penbutolol is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity.

Indications

Penbutolol is indicated in the treatment of mild to moderate arterial hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.Penbutolol is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity.

Definition

ChEBI: Penbutolol is a member of ethanolamines.

Manufacturing Process

21.8 g (0.1 mol) of 1,2-epoxy-3-(2'-cyclopentylphenoxy)propane, boiling at 113°C to 115°C/0.2 mm Hg (prepared from 2-cyclopentylphenol and epichlorhydrin in the presence of alkali) were dissolved in 250 ml of ethanol; to this solution, there were added dropwise, while stirring.8.9 g (0.15 mol) of t-butylamine. The reaction mixture was stirred for 2 hours at 60°C and then the solvent and the excess t-butylamine were removed by distillation. The residue which had been purified via the aqueous hydrochloride, crystallized, after removal of the ether by evaporation, upon rubbing or inoculation and yielded, after recrystallization from n-heptane, the 1-t-butylamino-2-hydroxy3-(2'-cyclopentylphenoxy)propane which was found to melt at 69°C to 70°C.

brand name

Levatol(Schwarz Pharma).

Therapeutic Function

Beta-adrenergic blocker

Pharmacokinetics

Penbutolol is a ?-1, ?-2 (nonselective) adrenergic receptor antagonist. Experimental studies showed a dose-dependent increase in heart rate in reserpinized (norepinephrine-depleted) rats given penbutolol intravenously at doses of 0.25 to 1.0 mg/kg, suggesting that penbutolol has some intrinsic sympathomimetic activity. In human studies, however, heart rate decreases have been similar to those seen with propranolol.

Safety Profile

Poison by ingestion and intravenous routes. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx.

Metabolism

Metabolized in the liver by hydroxylation and glucuroconjugation forming a glucuronide metabolite and a semi-active 4-hydroxy metabolite.