Antiplatelet effect of Z-335, a new orally active and long-lasting thromboxane receptor antagonist

Eur J Pharmacol. 1998 Sep 11;357(1):53-60. doi: 10.1016/s0014-2999(98)00540-8.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / antagonists & inhibitors
  • Animals
  • Biphenyl Compounds / pharmacology
  • Cilostazol
  • Drug Interactions
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use
  • Guinea Pigs
  • Heptanoic Acids / pharmacology
  • Humans
  • Indans / pharmacology*
  • Indans / therapeutic use
  • Male
  • Mice
  • Mice, Inbred ICR
  • Phenylacetates / pharmacology
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Pulmonary Embolism / chemically induced
  • Pulmonary Embolism / prevention & control
  • Receptors, Thromboxane / antagonists & inhibitors*
  • Receptors, Thromboxane / metabolism
  • Sulfonamides / pharmacology
  • Tetrazoles / pharmacology
  • Vasoconstrictor Agents

Substances

  • Biphenyl Compounds
  • Fibrinolytic Agents
  • Heptanoic Acids
  • Indans
  • Phenylacetates
  • Platelet Aggregation Inhibitors
  • Receptors, Thromboxane
  • Sulfonamides
  • Tetrazoles
  • Vasoconstrictor Agents
  • Z 335
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • vapiprost
  • Cilostazol
  • daltroban