title: Improved delivery through biological membranes. LVI. Pharmacological evaluation of alprenoxime--a new potential antiglaucoma agent.
abstract: A new site-specific chemical delivery system (CDS) for alprenolol was designed and investigated as a potential novel antiglaucoma agent. The effect of this compound, alprenoxime (AO), on the intraocular pressure (IOP) of rabbits was evaluated after its uni- and bilateral administration. AO produced significant reduction of the IOP starting at 30 min and lasting for more than 6 hr after its topical administration. Both in rats and in rabbits the i.v. bolus injection of AO (6 mg/kg) led to insignificant transient bradycardia, while no activity was found after oral or topical administration. Alprenolol (ALP) in a similar dose produced a sustained and significant bradycardia for more than 30 min. When the beta-adrenergic blocking activity was assessed against isoprenaline-tachycardia, the same results were obtained, i.e., AO led to a transient brief activity, whereas ALP produced a significant long-lasting beta blockade. These results support the potent ocular hypotensive action and the weak systemic beta-adrenergic blocking and cardiovascular activity of AO: a significant improvement in the therapeutic index. This finding recommends alprenoxime as a potent site-specific antiglaucoma agent with minimal systemic side effects.
authors.affiliation: Center for Drug Discovery, College of Pharmacy, University of Florida, Gainesville 32610.
authors.forename: N
authors.initials: N
authors.lastname: Bodor
authors.forename: A
authors.initials: A
authors.lastname: Elkoussi
mesh_terms: D000526:Alprenolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016503:Drug Delivery Systems; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007429:Intraocular Pressure / Q000187:drug effects*; D007545:Isoproterenol; D008297:Male; D009883:Ophthalmic Solutions; D010091:Oximes / Q000008:administration & dosage* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D009883:Ophthalmic Solutions; D010091:Oximes; C073472:alprenoxime; D000526:Alprenolol; D007545:Isoproterenol