Effects of antiglaucoma drugs GLC756, a novel dopamine D2 agonist and D1 antagonist, and timolol on endotoxin-induced TNF-alpha release in serum of rats

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Anti-inflammatory activity of an antiglaucoma drug may be an advantage for long-term treatment of glaucoma since it may reduce the risk of treatment-related inflammatory processes in outer compartments of the eye and probably also prevent or delay progression of glaucomatous retinal neurodegeneration. In this study, the effect of GLC756, a novel mixed dopamine D2 receptor agonist and dopamine D1 receptor antagonist, and timolol on endotoxin-induced cytokine tumor necrosis factor-α (TNF-α) release in serum was examined.


For endotoxin-induced TNF-α release, 8-week-old Lewis rats were intravenously injected with 160 μg lipopolysaccharide (LPS) from Salmonella typhimurium. GLC756, timolol, or betamethasone were either systemically (1 mg/kg SC for 5 days) or topically (0.4%, 0.5%, and 0.1%, respectively, 20 μL eye drops given 16 times over 48 hours in left and right eye) administered. TNF-α was measured in serum 2 and 48 hours after LPS induction.


A marked TNF-α increase in serum was found 2 hours after LPS induction. Administration of GLC756 and betamethasone, systemically and topically, decreased TNF-α release. However, due to large scattering of mean values only the effect of systemically administered GLC756 was statistically significant. In contrast, timolol increased TNF-α values stronger than LPS alone.


The significant suppression of LPS-induced TNF-α increase by GLC756 suggests an additional anti-inflammatory potential of the dopaminergic compound in the treatment of glaucoma. (Eur J Ophthalmol 2006; 16: 401-6)

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