Effects of topical nipradilol, a [beta] blocking agent with [alpha] blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans

Nipradilol is a non-selective β blocker with α₁ blocking and nitroglycerin-like vasodilating activities that are attributed to its nitroxyl moiety. 1-3 It has been registered as a systemic hypotensive drug. 4 The in vitro β blocking activity of nipradilol is approximately twice that of propranolol, 1 the α ₁ blocking activity about one fifth that of phentolamine, 2 and the nitroglycerin-like vasodilating activity is approximately one fifth that of nitroglycerin. 2 Some α₁ blockers and nitroglycerin are reported to reduce intraocular pressure (IOP) in experimental animals or normal humans by increasing uveoscleral outflow or tonographic outflow for at least a short period of time. 5-13 A highly selective α₁ blocker, bunazosin, reduced IOP in glaucoma patients by about 4 mm Hg for 1 year without producing tachyphylaxis. 14

The α₁ blocking and nitroglycerin-like activities of nipradilol might further enhance the ocular hypotensive effect owing to its β blocking activity, which is expected to reduce aqueous production. Further, the α₁ blocking and nitroglycerin-like vasodilating activities of nipradilol might provide an advantage over other β blockers that do not have such effects on ocular circulation. In a previous study, we found that the hypotensive effect of a single instillation of 0.25% nipradilol was significantly greater than that of 0.5% timolol in rabbit eyes. In rabbit eyes, the IOP lowering effect is attributed to both a decrease in aqueous humour production and an increase in uveoscleral outflow, and 2 weeks twice daily administration of 0.25% nipradilol might have beneficial effects on optic nerve head tissue circulation. 15

To further evaluate the potential of topical nipradilol as a new antiglaucoma drug, we examined the effect of topical nipradilol on IOP and aqueous humour dynamics in normal human eyes. We also performed a preliminary clinical study in a group of patients with ocular hypertension to examine the clinical potential of nipradilol.

Material and methods

NORMAL HUMAN VOLUNTEERS

The study population consisted of a total of 23 normal volunteers ranging in age from 31 to 49 years without a history of ocular disease. Before admission into the study, written consent was obtained from each subject after the nature of the study was fully explained. Before treatment, a medical history was taken and a complete ophthalmological...