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Abstract #13900 Published in IGR 8-2
Effects of antiglaucoma drugs GLC756, a novel dopamine D2 agonist and D1 antagonist, and timolol on endotoxin-induced TNF-α release in serum of rats
Laengle UW; Markstein R; Schneider V; Roman DEuropean Journal of Ophthalmology 2006; 16: 401-406
PURPOSE: 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 D 2 receptor agonist and dopamine D 1 receptor antagonist, and timolol on endo-toxin-induced cytokine tumor necrosis factor- a (TNFα) release in serum was examined. METHODS: For endotoxin-induced TNF- a 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 microL eye drops given 16 times over 48 hours in left and right eye) administered. TNF- a was measured in serum 2 and 48 hours after LPS induction. RESULTS: A marked TNF- a increase in serum was found 2 hours after LPS induction. Administration of GLC756 and betamethasone, systemically and topically, decreased TNFα release. However, due to large scattering of mean values only the effect of systemically administered GLC756 was statistically significant. In contrast, timolol increased TNFα values stronger than LPS alone. CONCLUSIONS: The significant suppression of LPS-induced TNFα increase by GLC756 suggests an additional anti-inflammatory potential of the dopaminergic compound in the treatment of glaucoma.
Dr. U.W. Laengle, Department of Toxicology/Pathology, Novartis Pharma AG, Basel, Switzerland
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
