Effect of 5-MCA-NAT, a putative melatonin MT₃ receptor agonist, on intraocular pressure in glaucomatous monkey eyes

Purpose: 5-MCA-NAT, a putative melatonin MT₃ receptor agonist, reduced intraocular pressure (IOP) in ocular normotensive rabbit eyes. This study evaluates the effect of topical application of 5-MCA-NAT on IOP in monkey eyes with laser-induced unilateral glaucoma. Methods: A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 25-μL drop of 5-MCA-NAT (2%) was applied topically to the glaucomatous eye at 9:30 AM and 3:30 PM for 5 consecutive days. IOP was measured hourly for 6 hours beginning at 9:30 AM for one baseline day, one vehicle-treated day, and treatment days 1, 3, and 5 with 5-MCA-NAT. Results: Compared with vehicle treatment, twice daily administration of 5-MCA-NAT for 5 days reduced (P < 0.05) IOP from 1 hour to 5 hours after the first dose, and the IOP-lowering effects were shown to last at least 18 hours following administration, based on IOP measurements made after the fourth and eighth doses. The ocular hypotensive effect of 5-MCA-NAT was enhanced with repeated dosing. The maximum reduction (P < 0.001) of IOP occurred at 3 hours after each morning dose, and was 4.0 ± 0.5 (mean ± SEM) mm Hg (10%) on day 1, 5.6 ± 0.8 mm Hg (15%) on day 3, and 7.0 ± 1.1 mm Hg (19%) on day 5. Adverse ocular or systemic side effects were not observed during the 5 days of treatment. Conclusions: 5-MCA-NAT, a putative melatonin MT₃ receptor agonist, reduces IOP in glaucomatous monkey eyes. Melatonin agonists with activity on the putative MT₃ receptor may have clinical potential for treating elevated IOP.