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Effects of latanoprost on rodent intraocular pressure
Affiliation:1. Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan;2. Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan;3. Department of Drug Absorption and Pharmacokinetics, Tohoku Pharmaceutical University, Sendai, Japan
Abstract:The aim of the present study was to evaluate the effects of the prostaglandin F analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes. Rodents have been increasingly used in glaucoma research; however, conflicting results regarding the actions of prostaglandins on rodent IOP have been published. In Wistar rats, a single dose of latanoprost (60 ng) produced a biphasic change in IOP: an initial rise in pressure (2.1 ± 0.7 mmHg) peaking at 2 h, followed by a prolonged hypotension with a peak reduction in IOP (5.2 ± 0.7 mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose-related with ED50 values of 108 and 5.2 ng, respectively. These responses were antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6 mice, a single dose of latanoprost also produced a biphasic response in IOP with an initial rise in pressure peaking between 1 and 2 h, followed by prolonged hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP response to topical latanoprost is characterized by an initial hypertension followed by a prolonged hypotension. This prolonged hypotension is similar to that measured in monkeys and humans. Taken together, these results support the idea that rodents can serve as in vivo models to study the actions of ocular hypotensive agents, such as prostaglandins.
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