Effect of 5-MCA-NAT, a Putative Melatonin MT3 Receptor Agonist, on Intraocular Pressure (IOP) in Glaucomatous Monkey Eyes

Abstract

Abstract: : Purpose: 5-MCA-NAT, a putative melatonin MT₃ receptor agonist, reduced IOP in rabbits. 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 a.m. and 3:30 p.m. for 5 consecutive days. IOP was measured hourly for 6 hrs beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and treatment days 1, 3, and 5 with 5-MCA-NAT. Results: Compared to vehicle treatment, twice daily administration of 5-MCA-NAT for 5 days reduced (p<0.05) IOP from 1 hr to 5 hrs after the first dose, and lasted at least 18 hrs after the fifth dose. The ocular hypotensive effect of 5-MCA-NAT was enhanced with repeated dosing. The maximum reduction (p<0.001) of IOP occurred at 3 hrs after each morning dose, and was 4.0 ± 0.5 (mean ± SEM) mmHg (10%) on day 1, 5.6 ± 0.8 mmHg (15%) on day 3, and 7.0 ± 1.1 mmHg (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 analog, reduces IOP in glaucomatous monkey eyes. Melatonin agonists with activity on the putative MT₃ receptor may have clinical potential for treating elevated IOP.

Keywords: animal model • intraocular pressure • pharmacology