z-335 and vapiprost

We investigated the pharmacological characteristics of Z-335 ((+/-)-sodium[2-[4-(chlorophenylsulfonylaminomethyl)indan-5-yl]ace tate monohydrate), a new indan derivative. Z-335 inhibited the specific binding of [3H]SQ-29548 to human platelets and guinea pig platelet membranes. The IC50 values of Z-335 for human platelets and guinea pig platelet membranes were 29.9 +/- 3.1 nM with a slope of 1.09 +/- 0.05 and 32.5 +/- 1.7 nM with a slope of 1.07 +/- 0.02, respectively. Z-335 inhibited thromboxane A2 receptor-mediated human and guinea pig platelet aggregation in vitro and oral administration of this drug to guinea pigs inhibited U-46619- and collagen-induced platelet aggregation for 24 h. Z-335 dose-dependently prevented the occurrence of U-46619-induced pulmonary thromboembolism in mice and the protective effect of this drug (0.3 and 3 mg/kg, p.o.) lasted for 24 h. These results strongly suggest that Z-335 is a potent, orally active and long-lasting thromboxane A2 receptor antagonist, which may be useful as an antiplatelet drug.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Biphenyl Compounds; Cilostazol; Drug Interactions; Fibrinolytic Agents; Guinea Pigs; Heptanoic Acids; Humans; Indans; Male; Mice; Mice, Inbred ICR; Phenylacetates; Platelet Aggregation; Platelet Aggregation Inhibitors; Pulmonary Embolism; Receptors, Thromboxane; Sulfonamides; Tetrazoles; Vasoconstrictor Agents