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• W1982394920 abstract "Glucocorticoids exert their actions via the glucocorticoid receptor through at least 2 intracellular mechanisms, known as transrepression and transactivation. It has been hypothesized that transrepression is the basis of their anti-inflammatory effects, whereas transactivation has been assumed to cause their side effects. ZK209614, a recently identified, novel selective glucocorticoid receptor agonist, exerts strong transrepression and weak transactivation. The objective of this study was to determine whether its pharmacological effects can be dissociated from its side effects. For this, we employed in vitro assays and topical in vivo models.ZK209614 and dexamethasone were used in in vitro transrepression and transactivation assays. To evaluate anti-inflammatory and antiallergic activities in vivo, ZK209614 and betamethasone phosphate were tested in the carrageenan-induced conjunctivitis model and allergic conjunctivitis model in rats. To evaluate side effects in vivo, treatments with ZK209614 and betamethasone phosphate were tested for the ocular hypertensive effects in a feline model, each drug being administered topically.ZK209614 showed strong transrepression and weak transactivation in the in vitro assays. When given as eyedrops, ZK209614 and betamethasone phosphate each had an inhibitory effect on edema weight in the rat carrageenan-induced conjunctivitis model. In the rat allergic conjunctivitis model, ZK209614 reduced the elevated vascular permeability at a concentration of 0.1%. In the feline intraocular pressure (IOP)-elevation experiment, topically administered betamethasone phosphate elevated IOP, but ZK209614 had no effect on IOP.The present investigations suggest that ZK209614 eyedrops have both anti-inflammatory and antiallergic effects, but no unwanted IOP-elevating effect. On that basis, ZK209614 might be a promising candidate as an ophthalmic drug with a better therapeutic index than classic glucocorticoids." @default.
• W1982394920 created "2016-06-24" @default.
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• W1982394920 date "2011-08-01" @default.
• W1982394920 modified "2023-09-24" @default.
• W1982394920 title "Beneficial Pharmacological Effects of Selective Glucocorticoid Receptor Agonist in External Eye Diseases" @default.
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• W1982394920 doi "https://doi.org/10.1089/jop.2010.0177" @default.
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