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Maria Caballo Gonzalez, Carmen del Campo, Loreto Salazar, Vanessa Andres-Guerrero, Marta Vicario de la Torre, Rocio Herrero-Vanrell, Irene Molina-Martínez; Ocular Hypotensive Activity Of A New Melatonin Analog OPD-11, In Normotensive Rabbits. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1992.
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The main risk factor in the development of glaucoma is an elevated intraocular pressure (IOP). It has been shown that the topical application of melatonin analogs, such as 5-MCA-NAT, can effectively reduce IOP. OPD-11 is a new melatonin analog able to decrease IOP in normotensive rabbits. The role of dissacharides, as protectant compounds against cells dissecation, has been previously investigated. The aim of this work was to prepare new ophthalmic formulations of OPD-11 (100 µM) containing fructose (F) or trehalose (T) to be administered by topical route. In vitro tolerance and in vivo efficacy of these formulations were also determined.
Two formulations were prepared. OPD-11 was first dissolved in propylene glycol and then diluted with an isotonic solution with F or T. Final formulations were composed of OPD-11 (100 µM) and F 2% or T 2% (OPD-11/F and OPD-11/T, respectively). Osmolarity, viscosity, surface tension and pH were assessed. In vitro cytotoxicity was evaluated in normal human conjunctival cells at different exposure times (15 min, 1 h and 4 h). The ocular hypotensive effect was evaluated after instillation (25 µL) in normotensive rabbits (n=20 eyes) for 8 h. As control, animals received vehicle without OPD-11. All the in vivo experiments were conducted in compliance with the ARVO statements for the Use of Animals in Ophthalmolgy and Vision Research.
OPD-11/F and OPD-11/T showed pH values nearly neutral, were within the range of isotonicity and satisfied the requirements of surface tension and viscosity for ophthalmic solutions. Cytotoxicity assays showed good tolerance in conjunctival cells for both formulations (cell viability>80% at all exposure times). OPD-11/F and OPD-11/T were able to maintain a hypotensive activity providing similar effects. Non significant differences were found between the maximum IOP reduction reached by both formulations (p>0.05; OPD-11/F: 21.32 ± 4.7%, OPD-11/T: 20.70 ± 3.7%). The hypotensive activity lasted 5h and 6h for OPD-11/F and OPD-11/T, respectively. The time of maximum effect was 3 hours in both cases.
Formulations containing the new agent OPD-11 (100 µM) and fructose or trehalose (2%) showed suitable properties for topical ophthalmic application. Besides, both formulations were capable of providing a hypotensive effect in normotensive rabbits. OPD-11 should be considered potentially useful in the treatment of glaucoma.
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