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JJ Pintor, T Pelaez, CH V Hoyle, A Peral; Melatonin Analogues Modulate Rabbit Intraocular Pressure . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4078.
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Purpose:To determine the effects of melatonin receptor agonists and antagonists on intraocular pressure (IOP). Methods:Rabbits were kept under controlled 12 h/12 h light/ dark cycles. IOP was measured by means of a Tonopen contact tonometer. Agents were applied topically (10-12 M 10-2 M), unilaterally, to the cornea in volumes of 10 µL. The contralateral eye received the same volume of saline solution. Melatonin and its analogues, were used to establish dose-response curves. IOP was measured at 0.5, 1, 2, 3, 4, 5 and 6 hours after the application. Antagonist studies were performed by applying a dose of 5-MCA-NAT and graded doses of luzindole, DH-97, 4-P-PDOT and prazosin ranging from 10-12 M to 10-2 M 30 min before application of the agonist. Results:Melatonin, 2-Phe-melatonin, 6-Cl-melatonin, 2-I-melatonin, 5-MCA-NAT and N-acetylserotonin reduced IOP, the most effective compound being 5-MCA-NAT which reduced IOP to 65%. The pD2 values for the compounds were: melatonin, 7.860.30; 2-Phe-melatonin, 7.250.18; 6-Cl-melatonin, 7.580.05; 2-iodo-melatonin, 7.560.89; 5-MCA-NAT, 7.430.30; N-acetyl-melatonin, 7.970.30. Antagonists reversed the effect of melatonin and 5-MCA-NAT, among them prazosin presented a pA2 value of 8.490.17. Luzindole, DH-97 and 4-P-PDOT also antagonised the effects of melatonin, being active in the micromolar range. Conclusion:Melatonin receptor agonists, such as the selective MT3 receptor agonist 5-MCA-NAT may be useful for the treatment of those pathologies presenting with an elevated intraocular pressure such as glaucoma.
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