Improved delivery through biological membranes. LVI. Pharmacological evaluation of alprenoxime--a new potential antiglaucoma agent.

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.