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Abstract #11265 Published in IGR 6-3

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

Serle JB; Wang RF; Peterson WM; Plourde R; Yerxa BR
Journal of Glaucoma 2004; 13: 385-388

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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) 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 agonist, reduces IOP in glaucomatous monkey eyes. Melatonin agonists with activity on the putative MT3 receptor may have clinical potential for treating elevated IOP.

Dr. J. Serle, Mount Sinai School of Medicine, New York, NY 10029, USA. janet.serle@mssm.edu

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5 Experimental glaucoma; animal models

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