Effects of topical nipradilol, a beta-blocking agent with alpha-blocking and nitroglycerin-like activities, on aqueous humor dynamics and fundus circulation.
OBJECTIVE
To study the effects of nipradilol, a nonselective beta-blocker with alpha 1-blocking activity and nitroglycerin-like activity, on aqueous humor dynamics and optic nerve head (ONH) circulation in albino rabbits.


METHODS
Experiments were carried out during the dark phase, in conscious rabbits conditioned to a schedule of alternating 12-hour periods of light and dark. The blood-aqueous barrier permeability and the aqueous flow rate were determined fluorophotometrically. The effect on outflow to general blood circulation and uveoscleral outflow were determined by using the fluorophotometric Diamox technique, and the effect on the uveoscleral outflow was further assessed by using the anterior chamber perfusion method. The ONH circulation was estimated by using the laser speckle method.


RESULTS
Unilateral topical administration 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 effects. Single instillation of 0.25% nipradilol showed no significant effect on blood-aqueous barrier permeability and decreased aqueous flow rate in the treated eye (17%; P < 0.01) and in the contralateral eye (9%, P < 0.05). Nipradilol produced no significant effect on outflow facility to general blood circulation, whereas it substantially increased uveoscleral outflow. Twice-daily 0.25% nipradilol instillation increased 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 nerve head circulation in rabbits, further studies are warranted to determine whether nipradilol has potential as an antiglaucoma agent in humans.
Kanno
M
M
Department of Ophthalmology, University of Tokyo School of Medicine, Japan.
Araie
M
M
Tomita
K
K
Sawanobori
K
K
D000287:Administration, Topical; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001775:Blood Circulation / Q000187:drug effects*; D001783:Blood Flow Velocity; D018916:Blood-Aqueous Barrier / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015590:Fluorophotometry; D005654:Fundus Oculi; D007429:Intraocular Pressure / Q000187:drug effects; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D009898:Optic Disk / Q000098:blood supply; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012590:Sclera / Q000098:blood supply; D013999:Timolol / Q000494:pharmacology; D014602:Uvea / Q000098:blood supply; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D014665:Vasodilator Agents; D013999:Timolol; C036089:nipradilol; D005996:Nitroglycerin