FP and EP2 prostanoid receptor agonist drugs and aqueous humor outflow devices for treating ocular hypertension and glaucoma

Exp Eye Res. 2023 Feb 18:109415. doi: 10.1016/j.exer.2023.109415. Online ahead of print.ABSTRACTProstaglandin (PG) receptors represent important druggable targets due to the many diverse actions of PGs in the body. From an ocular perspective, the discovery, development, and health agency approvals of prostaglandin F (FP) receptor agonists (FPAs) have revolutionized the medical treatment of ocular hypertension (OHT) and glaucoma. FPAs, such as latanoprost, travoprost, bimatoprost, and tafluprost, powerfully lower and control intraocular pressure (IOP), and became first-line therapeutics to treat this leading cause of blindness in the late 1990s to early 2000s. More recently, a latanoprost-nitric oxide (NO) donor conjugate, latanoprostene bunod, and a novel FP/EP3 receptor dual agonist, sepetaprost (ONO-9054 or DE-126), have also demonstrated robust IOP-reducing activity. Moreover, a selective non-PG prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI), was discovered, characterized, and has been approved in the United States, Japan and several other Asian countries for treating OHT/glaucoma. FPAs primarily enhance uveoscleral (UVSC) outflow of aqueous humor (AQH) to reduce IOP, but cause darkening of the iris and periorbital skin, uneven thickening and elongation of eyelashes, and deepening of the upper eyelid sulcus during chronic treatment. In contrast, OMDI lowers and controls IOP by activation of both the UVSC and trabecular meshwork outflow pathways, and it has a ...
Source: Experimental Eye Research - Category: Opthalmology Authors: Source Type: research