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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

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

U W Laengle, R Markstein, V Schneider, D Roman

Eur J Ophthalmol. May-Jun 2006;16(3):401-6.

PMID: 16761241

Abstract:

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-alpha (TNF-alpha) release in serum was examined.
Methods:
For endotoxin-induced TNF-alpha release, 8-week-old Lewis rats were intravenously injected with 160 microg 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-alpha was measured in serum 2 and 48 hours after LPS induction.
Results:
A marked TNF-alpha increase in serum was found 2 hours after LPS induction. Administration of GLC756 and betamethasone, systemically and topically, decreased TNF-alpha release. However, due to large scattering of mean values only the effect of systemically administered GLC756 was statistically significant. In contrast, timolol increased TNF-alpha values stronger than LPS alone.
Conclusions:
The significant suppression of LPS-induced TNF-alpha increase by GLC756 suggests an additional anti-inflammatory potential of the dopaminergic compound in the treatment of glaucoma.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP30165970	Timolol Related Compound D		30165-97-0	Price

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