Abstract
Abstract: :
Purpose: The prostamides are members of the fatty acid amide family and are biosynthesized from anandamide (Yu et al., J. Biol Chem 272, 21181, 1997; Burstein et al, PGs and Other Lipid Med 61, 29, 2000). The purpose of this study was to compare the activity of those prostamides described to date (prostamides D2, E2, and F2α) on intraocular pressure. Methods: Intraocular pressure was measured by pneumatonometry in cynomolgus monkeys rendered unilaterally ocular hypertensive by circumferential laser treatment. The ocular hypertensive eye was treated once daily with a 0.03% dose of each prostamide or a 0.1% dose of anandamide or α-methyl anandamide for 5 days. Intraocular pressure in both eyes was recorded on treatment days 1, 3, and 5. Results: Prostamides D2, E2 and F2α were similar in their ocular hypotensive activities. Thus, prostamides D2, E2 and F2α at a 0.03% topical dose, reduced glaucomatous monkey intraocular pressure by 20%, 25% and 23.4% at peak effect, respectively. The degree of ocular hypotensive activity achieved with the prostamides was similar to that produced by anandamide and α-methyl anandamide (0.1%). Conclusion: Prostamides are efficacious ocular hypotensive agents. Anandamide, which is pharmacologically a CB and VR receptor agonist, also lowers intraocular pressure. Pharmacologically prostamides and anandamide are distinct. Since, however, anandamide is also the precursor of the prostamides, the relative involvement of prostamide formation, CB receptors, and VR receptors in anandamide induced ocular hypotension remains to be elucidated.
Keywords: 541 receptors: pharmacology/physiology • 514 pharmacology • 444 intraocular pressure