Y-33075 (Y-39983 free base) is a ROCK inhibitor that lowers intraocular pressure (IOP), increases blood flow to the optic nerve head (ONH), and increases the number of RGCs (retinal ganglion cells) in the body with regenerating axons.

The in vitro activity of Y-33075 was evaluated in cultured human umbilical vein endothelial cells (HUVECs). After seeding, HUVECs were treated with medium containing Y-33075 (1 μM) for 15 or 30 minutes. The cells exhibited contraction after treatment, but their morphology recovered within 1 hour after the removal of Y-33075. These results indicate that Y-33075 induces endothelial cell contraction, suggesting a potential effect on vascular barrier function [1].

In rabbits, a single 50 μL dose of Y-33075 (0.003%–0.1%) reduced IOP by up to 13.2 ± 0.6 mmHg (0.1%, 2 h), and repeated dosing (0.03%, 4×/day for 28 days) maintained a 7.0–9.6 mmHg reduction. In monkeys, 0.05% Y-33075 reduced IOP by 2.5 ± 0.8 mmHg at 3 h. Y-33075 also enhanced conventional outflow in rabbits (+65.5%), with minimal side effects except occasional subconjunctival hemorrhage at high dosing frequency [2].