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

Abstract

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-microL 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.

• Authors: Janet B Serle, Rong-Fang Wang, Ward M Peterson, Robert Plourde, Benjamin R Yerxa
• Journal: Journal of glaucoma (J Glaucoma) Vol. 13 Issue 5 Pg. 385-8 (Oct 2004) ISSN: 1057-0829 [Print] United States
• PMID: 15354076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 5-methoxycarbonylamino-N-acetyltryptamine
• Receptors, Melatonin
• Tryptamines

Topics

• Administration, Topical
• Animals
• Drug Administration Schedule
• Female
• Glaucoma (physiopathology)
• Intraocular Pressure (drug effects)
• Macaca fascicularis
• Receptors, Melatonin (agonists)
• Time Factors
• Tryptamines (administration & dosage, pharmacology)