Latanoprost Xalatan

Structural Formula

Ball-and-Stick Model

Ball-and-Stick Model

= Hydrogen

= Carbon

= Hydrogen

=Oxygen

Year of discovery: Early 1990s; Year of introduction: 1996 (Pharmacia & Upjohn; now marketed by Pfizer); Drug category: Prostaglandin F2„ analog/Prostanoid selective FP receptor agonist; Main uses: To reduce eye-pressure in those with glaucoma or elevated eye-pressure; Related drugs: Bimatoprost (Lumigan), Travoprost (Travatan), Timolol (Timoptic).

Glaucoma is an eye condition that damages the optic nerve. Although initially asymptomatic, glaucoma leads to visual field loss and eventually blindness, if left untreated. Damage to the optic nerve is irreversible and irreparable. Glaucoma is the second leading cause of vision loss worldwide. It is estimated that over 70 million people have the disease, but less than 50% are aware of it. There are several factors that may lead to glaucoma, including increased intraocular pressure (IOP), a family history of glaucoma, high blood pressure, diabetes, female gender, and possibly Asian or African-American lineage. Although increased IOP has not positively been linked to the onset of the disease, it is nonetheless a risk factor. Studies have shown that the reduction of IOP can delay glaucomatous nerve or visual field damage. Primary open angle glaucoma is the most prevalent form and it is caused by chronic obstruction of the outflow of aqueous humour within the trabecular meshwork (the primary aqueous drainage system of the eye).

Current treatment for glaucoma includes the use of drugs, surgery, and argon laser trabeculoplasty when drug treatment alone fails. Pharmacotherapies for glaucoma target the reduction of IOP by: (1) reduction of aqueous humour production and (2) elevation of the outflow of aqueous humour.1 The reduction of aqueous humour production can be achieved by the use of topical (3-blockers such as timolol (see structure at right), but the efficacy of this treatment decreases over time.

(The oral form of timolol is used to treat high blood pressure and prevent heart attack.)

Prostaglandin analogs such as latanoprost (Pharmacia & Upjohn) are now the most successful drugs for decreasing IOP by raising the outflow of aqueous humour.2 Latanoprost is a prodrug which is hydrolyzed in the cornea by esterases which cleave the isopropyl ester moiety (red). The resulting biologically active carboxylic acid binds to ocular PG receptors, leading to an increase in the outflow of aqueous humour and a lowering of IOP. The structures of two other efficacious ocular prostaglandin analogs, bimatoprost (Lumigan™, Allergan) and travoprost (Travatan™, Alcon), are shown below.3

O oh

chj ch3

Timolol (Timoptic™)

Bimatoprost (Lumigan1

Travoprost (Travatan11

Bimatoprost (Lumigan1

Travoprost (Travatan11

1. Ther. Clin. Risk Manag. 2006, 2, 193-205; 2. Drugs & Aging 2003, 20, 597-630; 3. Curr. Med. Res. Opin. 2005, 21, 1875-1883; Rets. p. 106

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