Netarsudil

Netarsudil (AR-13324) is a competitive inhibitor of Rho-associated protein kinases (ROCK I and ROCK II) and a reversible inhibitor of the norepinephrine transporter (NET). Netarsudil reduces intraocular pressure by inhibiting ROCK, causing relaxation of trabecular meshwork cells and dilation of episcleral veins, thereby increasing the ease of aqueous humor outflow, while inhibiting NET to reduce aqueous humor production. Netarsudil is mainly used in the study of ocular hypertension and primary open-angle glaucoma^[1][2][3][4]. In Vitro:Netarsudil exerts its effects by metabolizing to the active compound Netarsudil-M1. Netarsudil-M1 (0.3 μM; 3 h) significantly increases aqueous humor outflow ease in human ocular tissue perfusion experiments and increases effective filtration length (PEFL) by dilating the trabecular meshwork (TM) and episcleral veins (ESV)^[1]. In Vivo:Netarsudil (0.04% ophthalmic solution; topical instillation; single dose) increases aqueous humor outflow ease and reduces aqueous humor production after 6 hours of treatment in female cynomolgus monkeys, exerting an ocular hypotensive effect^[2].
Netarsudil (0.04% eye drops; topical instillation; once daily; 3 days) significantly reduces intraocular pressure and episcleral venous pressure in male Dutch DB rabbits without affecting arterial pressure, heart rate, and carotid blood flow^[3].