LEVOBUNOLOL

Absorption

80%

Toxicity

Bradycardia, hypotension, bronchospasm, and acute cardiac failure, LD50=700 mg/kg (orally in rat).

Chemical properties

White Solid

Originator

Betagan,Allergan,India

The Uses of LEVOBUNOLOL

As a non-selective adrenoceptor antagonist, Levobunolol is used as an anticonvulsant.

The Uses of LEVOBUNOLOL

Levobunolol hydrochloride is an antiglaucoma agent in ophthalmie solutions.

Background

A nonselective beta-adrenoceptor antagonist used in the treatment of glaucoma.

Indications

For lowering intraocular pressure (IOP) and may be used in patients with chronic open-angle glaucoma or ocular hypertension.

Definition

ChEBI: A cyclic ketone that is 3,4-dihydronaphthalen-1-one substituted at position 5 by a 3-(tert-butylamino)-2-hydroxypropoxy group (the S-enantiomer). A non-selective beta-adrenergic antagonist used (as its hydrochlo ide salt) for treatment of glaucoma.

Manufacturing Process

9.62 g (59 mmoles) 5-hydroxy-3,4-dihydro-1(2H)-naphthalenone, 67 ml toluene, 0.36 g (1.1 mmoles) tetra-n-butylammonium bromide, 4.51 g (68 mmoles) 85% potassium hydroxide and 20 ml (254 mmoles) (R)-(-)- epichlorhydrine were placed in an appropriate flask fitted with efficient mechanical stirring, and the mixture was heated under reflux for two hours. The mixture was allowed to cool to 30°C, 50 ml toluene and 50 ml water were added and the mixture was vigorously stirred. The organic phase was removed and the aqueous phase extracted with 25 ml toluene. The combined organic phases were concentrated at reduced pressure, 31 ml (300 mmoles) tert-butylamine, 45 ml ethanol and 3 ml deionized water were added, and the solution was heated under reflux for one hour. The mixture was allowed to cool to 40°C and the volatile products were distilled at reduced pressure. Toluene (9 ml) was added to the residue and volatiles were distilled at reduced pressure. (S)-5-(2,3-Epoxypropoxy)-3,4-dihydro-1(2H)- naphthalenone with an optical purity greater than 95% was obtained. Toluene (75 ml) was added to the product, and then, 10 ml of 35% (w/v) hydrochloric acid and 110 ml water, and the mixture was stirred for fifteen minutes. The organic phase was decanted and the aqueous one was extracted with 50 ml toluene. The aqueous phase was basified by addition of a solution of 5.1 g sodium hydroxide in 150 ml water and extracted twice with toluene (100 and 50 ml, respectively). The combined organic extracts were dried with anhydrous sodium sulfate, decolorized with active charcoal and filtered.
To the above toluenic solution containing levobunolol as free base, 16 ml ethanol and the stoichiometric amount of hydrogen chloride were added. The stirred mixture was cooled below 10°C and kept at this temperature for one hour. The precipitated solid was filtered, washed with toluene, recrystallized twice from 43 ml ethanol and dried to give 10.0 g (51% yield) of (-)-3,4- dihydro-5-(3-(tert-butylamino)-2-hydroxypropoxy)-1(2H)-naphthalenone hydrochloride (levobunolol hydrochloride) having a rotary power at 25°C below -19°.

brand name

Akbeta(Akorn); Betagan(Allergan).

Therapeutic Function

Beta-adrenergic blocker

Pharmacokinetics

Levobunolol is an ophthalmic beta-blocker, equally effective at β(1)- and β(2)-receptor sites. Levobunolol reduces both elevated and normal IOP in patients with or without glaucoma. In patients with elevated IOP, levobunolol reduces mean IOP by approximately 25-40% from baseline. As the drug is a nonselective &beta-adrenergic blocking agent, it can produce both systemic pulmonary and cardiovascular effects following topical application to the eye. These effects include adverse pulmonary effects (eg. bronchoconstriction, increased airway resistance), and a decrease in blood pressure and heart rate.

Metabolism

Hepatic