Synthesis and Pharmacological Activity of Adaprolol Enantiomers: A New Soft Drug for Treating Glaucoma

ABSTRACT

Adaprolol maleate is a new β-adrenergic antagonist that is being developed to treat glaucoma. The soft drug was designed to minimize systemic activity through facile inactivation to an inactive metabolite. Studies with other potent β-adrenergic antagonists indicated that tissue specific receptor differences might be more stringent for selected β-adrenergic blocking activities and suggested that R enantiomers of traditional β-blockers should be developed for controlling glaucoma. The present studies demonstrate that the potent ocular hypotensive effects of adaprolol are not stereoselective. In contrast, cardiac effects could be detected after intravenous S(+) adaprolol, but not R(−) adaprolol. The studies confirm that adaprolol functions as a potent β-adrenergic antagonist. The neglible systemic β-blocking activity detected with ophthalmic administration of adaprolol is consistent with soft drug design.