Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies.

Cytotoxic concentrations of imatinib mesylate (10-50 microM) were required to trigger markers of apoptosis and endoplasmic reticulum stress response in neonatal rat ventricular myocytes and fibroblasts, with no significant differences observed between c-Abl silenced and nonsilenced cells. In mice, oral or intraperitoneal imatinib treatment did not induce cardiovascular pathology or heart failure. In rats, high doses of oral imatinib did result in some cardiac hypertrophy.

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).