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T.R. Dean, L.M. DeSantis, M. Hellberg, M.A. McLaughlin, V.L. Sallee, N. Sharif, J.A. May; The Role of Serotonin and Serotonergic Compounds in the Modulation of Intraocular Pressure in the Lasered Cynomolgus Monkey . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3205.
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Purpose: Serotonin's (5-HT) role in the modulating of aqueous humor dynamics is currently unknown. It is an important neurotransmitter in the eye, is present in aqueous humor and serotonergic neurons have been identified in key anterior segment tissues. Serotonin is a non-selective agonist for the numerous 5-HT subtypes. A pharmacological approach was used to study the action of serotonergic compounds on intraocular pressure (IOP) in the cynomolgus monkey and identify those receptors involved in the modulation of IOP. Methods: Serotonin and selective serotonergic agonists and antagonists of the 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 subtypes were dosed topically to the eyes of cynomolgus monkeys and IOP was measured at 1, 3 and 6 or 7 hours post dose. Results: Serotonin itself had only a modestly lowered IOP and the effect was short-lived. Selective compounds with agonist activity against the 5-HT1 family of receptors, 5-HT3, 5-HT4 and 5-HT7 were not associated with a lowering of IOP. Antagonists were equally ineffective. 5-HT2 antagonists lower IOP in this model but most of these compounds have significant α1 antagonist activity, which is believed to responsible for the hypotensive effect. Surprisingly, compounds with agonist activity at 5-HT2 receptors were found to be effective ocular hypotensive agents. In particular, alpha-methyl serotonin, a classical 5HT2 agonist, dose-dependently lowered IOP up to 30% when administered to hypertensive monkey eyes. Conclusion: Serotonin plays an important role in the regulation of IOP in the cynomolgus monkey and its hypotensive action is mediated through the activation of 5-HT2 receptors.
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