PMID: 8590263Jan 1, 1995Paper

Sequential bioactivation of methoxime analogs of beta-adrenergic antagonists in the eye

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
N BodorH Farag

Abstract

Selected beta-adrenoreceptor antagonists are the antiglaucoma drugs of first choice in most cases. However, a number of significant central nervous system (CNS), cardiovascular and respiratory side-effects following topical ocular installation of beta-blockers have also been reported. Site- and stereo-specific delivery to the eye of beta-blockers was achieved by application of a sequential bioactivation of the chemical delivery system (CDS) analogs of these drugs, which are converted to the active beta-blockers only in the eye, thus systemic side effects are avoided. The corresponding ketoxime analogs of the various beta-blockers were successfully applied and one of them, Alprenoxime, was tested in humans. The main problem with these compounds, however, is formulation stability: Alprenoxime has a t90 of only 2-3 months. Thus, alternate structures were searched. Methoxime analogs of selected beta-blockers were synthesized and their chemical stability established at different pH's. Subsequently, their in vivo sequential enzymatic conversion was confirmed using HPLC. Comparative intraocular pressure (IOP) reducing activity of the methoximes were then studied using normotensive rabbits. The methoxime analogs showed significantly im...Continue Reading

References

Nov 1, 1985·British Journal of Clinical Pharmacology·R Richards, A E Tattersfield
Jan 1, 1984·American Journal of Ophthalmology·R B SchoeneC H Beasley
Jan 1, 1980·Annals of the New York Academy of Sciences·P D WhangerC L Holcomb
Jun 1, 1984·Experimental Eye Research·N Bodor, G Visor

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Citations

Dec 17, 2015·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Venkata Kashyap Yellepeddi, Srinath Palakurthi
Jul 22, 2016·Expert Opinion on Drug Delivery·Pranjal TaskarSoumyajit Majumdar
Nov 5, 1997·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·N BodorL Prokai
Aug 29, 1997·Journal of Medicinal Chemistry·M F Sugrue

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