Netarsudil Dihydrochloride (AR-13324 Dihydrochloride) is an inhibitor of Rho-related protein kinase (ROCK) and norepinephrine transporter (NET) and is effective in reducing intraocular pressure (IOP).

METHODS: Primary PTM cells were incubated for 6 hours in the presence of 0, 0.015, 0.138 or 1.2 μM Netarsudil, then fixed and stained with Alexa Fluor-488 phalloidin and Hoechst 33342, Netarsudil dosage in actin stress fiber assay reaction.
RESULTS Netarsudil's ability to disrupt actin stress fibers and focal adhesions in PTM cells and HTM cells. [1]
METHODS: Serum-starved primary HTM cells were incubated for 24 hours in the presence of either vehicle, fixed and stained for fibrosis markers with 8 ng/mL human TGF-β2, 500 nM netarsudil or 8 ng/mL TGF-β2 plus 500 nM netarsudil. α-SMA, fibroblast-specific protein 1 (FSP1) and collagen 1A were used to explore the effect of Netarsudil on the profibrotic effect of TGF-β on HTM cells.
RESULTS Simultaneous treatment of HTM cells with TGF-β2 and Netarsudil abolished the induction of these markers by TGF-β2, indicating that Netarsudil has antifibrotic activity. [1]

METHODS: Netarsudil 0.04% was administered once to one eye per animal for 3 days, with the untreated eye serving as a control. After dosing each morning on days 1 and 3, before test article administration (time 0) and at 1, 2, 4, 8 and 24 hours (rabbit) or 4, 8 and 24 hours (monkey) Intraocular pressure in both eyes.
RESULTS Netarsudil 0.04% achieved greater IOP reduction and longer duration of efficacy. The greatest difference was seen 8 hours after dosing on Day 3, when Netarsudil 0.04% reduced IOP by 8.1 ± 0.7 mmHg. [1]