New insights into the pharmacological properties of potent antiplatelet 2-amino-benzo[d]isothiazol-3-one derivatives

Pharmacol Res. 2002 Nov;46(5):389-93. doi: 10.1016/s1043661802002086.

Abstract

A series of 2-amino-benzo[d]isothiazol-3-one derivatives (1-8), previously described as in vitro potent antiaggregatory agents endowed with spasmolytic properties, was evaluated for in vitro antiplatelet activity in guinea-pig platelet rich plasma and for in vivo effects on experimental thrombosis and bleeding time in mice. All the 2-amino-benzo[d]isothiazol-3-one derivatives 1-8 were more potent antiplatelets against collagen than acetylsalicylic acid and, unlike this drug, strongly inhibited thromboxane agonist U46619-induced aggregation. Subacutely administered (5mgkg(-1) day i.p. for 5 days), compounds 6 and 7 protected mice from collagen/epinephrine induced pulmonary thromboembolism at about 20-fold lower doses than acetylsalicylic acid and they prolonged bleeding time like the most part of the other derivatives. The potent antithrombotic activity was coupled with the absence of any lethal and ulcerogenic effect up to 200mgkg(-1) os.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Bleeding Time
  • Guinea Pigs
  • Ileum / physiology
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Lethal Dose 50
  • Male
  • Mice
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / physiology
  • Parasympatholytics / chemistry
  • Parasympatholytics / pharmacology*
  • Parasympatholytics / toxicity
  • Peptic Ulcer / chemically induced
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / toxicity
  • Pulmonary Embolism / prevention & control*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Thiazoles / toxicity

Substances

  • 2-amino-benzo(d)isothiazol-3-one
  • Parasympatholytics
  • Platelet Aggregation Inhibitors
  • Thiazoles