EFFECTS OF TOPICAL NIPRADILOL, A BETA-BLOCKING AGENT WITH ALPHA-BLOCKING AND NITROGLYCERIN-LIKE ACTIVITIES, ON AQUEOUS-HUMOR DYNAMICS AND FUNDUS CIRCULATION

PURPOSE. TO study the effects of nipradilol, a nonselective beta-block er with alpha(1)-blocking activity and nitroglycerin-like activity, on aqueous humor dynamics and optic nerve head (ONH) circulation in albi no rabbits. METHODS. Experiments were carried out during the dark phas e, in conscious rabbits conditioned to a schedule of alternating 12-ho ur periods of light and dark. The blood-aqueous barrier permeability a nd the aqueous flow rate were determined fluorophotometrically. The ef fect on outflow to general blood circulation and uveoscleral outflow w ere determined by using the fluorophotometric Diamox technique, and th e effect on the uveoscleral outflow was further assessed by using the anterior chamber perfusion method. The ONH circulation was estimated b y using the laser speckle method. RESULTS. Unilateral topical administ ration of 0.25% nipradilol solution lowered intraocular pressure (IOP) with relatively weak contralateral effects in a dose-dependent manner with a maximum reduction of 6 mm Hg and an effect duration of 6 hours . Twice-daily instillation for 14 days showed no attenuation of the ef fects, Single instillation of 0.25% nipradilol showed no significant e ffect on blood-aqueous barrier permeability and decreased aqueous flow fate in the treated eye (17%; P < 0.01) and in the contralateral eye (9%, P < 0.05). Nipradilol produced no significant effect on outflow f acility to general blood circulation, whereas it substantially increas ed uveoscleral outflow. Twice-daily 0.25% nipradilol instillation incr eased ONH tissue blood velocity by 13% (P < 0.01), which was probably attributable to locally penetrating drug. CONCLUSIONS. Because of its ability to lower IOP and to increase uveoscleral outflow and optic ner ve head circulation in rabbits, further studies are warranted to deter mine whether nipradilol has potential as an antiglaucoma agent in huma ns.