Antiglaucoma drug GLC756 and its effect on cellular cAMP and tumor necrosis factor alpha release in vitro of activated human monocytic leukemia cells.

Purpose: GLC756, a putative antiglaucoma drug with dopamine D(2) agonist and D(1) antagonist properties, significantly decreases tumor necrosis factor alpha (TNF-alpha) levels in lipopolysaccharide (LPS)-induced rats. The present study describes the effects of GLC756 on cellular adenosine 3', 5'-cyclic monophosphate (cAMP) in relation to TNF-alpha production on LPS-stimulated human acute monocytic leukemia cells.

Methods: A human peripheral blood acute monocytic leukemia cell line (THP-1) was activated via LPS.

Effects of latanoprost, timolol and GLC756, a novel dopamine D(2) agonist and D(1) antagonist on LTC(4) release after rat mast cell activation.

Purpose: Mast cells participate in ocular allergic inflammation by releasing biologically active mediators. Leukotrienes are released from activated mast cells via an IgE-dependent mechanism, and play a crucial role in ocular allergic inflammation. In this study, the effect of three topical antiglaucoma drugs, that is, latanoprost, timolol and GLC756, a novel dopamine D(2) agonist and D(1) antagonist, on leukotriene C(4) (LTC(4)) release after rat mast cell activation was examined.

Effect of GLC756, a novel mixed dopamine D1 receptor antagonist and dopamine D2 receptor agonist, on TNF-alpha release in vitro from activated rat mast cells.

Tumor necrosis factor-alpha (TNF-alpha) is released from activated mast cells via an IgE-dependent mechanisms, and plays a crucial role in ocular allergic inflammation. This study examined the influence of three antiglaucoma drugs differing in their chemical structure and pharmacological profile (i.e.

GLC756 decreases TNF-alpha via an alpha2 and beta2 adrenoceptor related mechanism.

GLC756, a polyvalent anti-glaucoma drug showed in an endotoxin-induced-uveitis model (EIU) in rats a significant tumor necrosis factor-alpha (TNF-alpha) decrease in serum, indicating an additional anti-inflammatory potential of this compound. The receptors on which GLC756 binds (D1, D2, D4, alpha-1, alpha-2, 5-HT1A, 5-HT2C, 5-HT1D, 5-HT2 A, beta-1, and beta-2) were suggested to play a role. In order to identify a receptor type mediating the TNF-alpha lowering response, GLC756 was combined with various counteracting compounds (CP).

Effects of antiglaucoma drugs timolol and GLC756, a novel dopamine D2 agonist and D1 antagonist, on endotoxin-induced-uveitis in rats.

Antiglaucoma drugs with anti-inflammatory properties may be of particular value for the long-term treatment of glaucoma since they may reduce the risk for treatment-related inflammatory processes in outer compartments of the eye. The purpose of this study was, to evaluate the effect of systemic and topical administration of GLC756, a novel mixed dopamine D(2) receptor agonist and D(1) receptor antagonist which lowered intraocular pressure in man, and timolol on endotoxin-induced-uveitis (EIU) in rats. For EIU, 8-week-old Lewis rats received an intravenous injection of 160 microg lipopolysaccharide (LPS) from Salmonella typhimurium.