title: Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on intraocular pressure in glaucomatous monkey eyes.
abstract: OBJECTIVE
  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.affiliation: Mount Sinai School of Medicine, New York, New York 10029, USA. janet.serle@mssm.edu
authors.forename: Janet B
authors.initials: JB
authors.lastname: Serle
authors.forename: Rong-Fang
authors.initials: RF
authors.lastname: Wang
authors.forename: Ward M
authors.initials: WM
authors.lastname: Peterson
authors.forename: Robert
authors.initials: R
authors.lastname: Plourde
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Yerxa
mesh_terms: D000287:Administration, Topical; D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D005901:Glaucoma / Q000503:physiopathology*; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D044094:Receptors, Melatonin / Q000819:agonists*; D013997:Time Factors; D014363:Tryptamines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C413586:5-methoxycarbonylamino-N-acetyltryptamine; D044094:Receptors, Melatonin; D014363:Tryptamines