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

Abstract

Aims: To study the effects of topical nipradilol, a non-selective beta blocker with alpha blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension.

Methods: Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0. 5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks.

Results: Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period.

Conclusion: Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new antiglaucoma drug.

Figure 1

Reduction in the intraocular pressure after 0.125%, 0.25% nipradilol, or 0.5% timolol instillation in drug treated eye and vehicle treated eye. Δ Intraocular pressure = difference between the change from pretreatment values in the drug treated experiment (0.125% or 0.25% nipradilol or 0.5% timolol solution instilled in one eye and vehicle in fellow eye) and that in the control experiment (vehicle solutions instilled in both eyes). Figures are significantly negative, *p<0.05. Bars represent mean (SE) (mm Hg) in 11 eyes of 11 subjects.

Figure 2

Intraocular pressure after twice daily instillation of 0.25% nipradilol during 8 weeks. Bars represent mean (SE) (mm Hg) in 24 eyes of 24 subjects. *Compared with week 0, v week 1; p=0.0016, v week 2; p=0.0022, v week 3; p<0.0001, v week 4; p<0.0001 (paired t test with Bonferroni's correction).