Comparison of in vitro and ex vivo antiplatelet effects of 1,2-benzisothiazolin-3-one and its 2-amino derivative.
The in vitro and ex vivo antiplatelet effects of 2-amino-1,2-benzisothiazolin-3-one (1) are compared with those of its parent compound 1,2-benzisothiazolin-3-one (2) and with acetylsalicylic acid (ASA) against different agonists. 2-Amino-1,2-benzisothiazolin-3-one inhibits adenosine diphosphate (ADP)-, arachidonic acid (AA)- and collagen-induced human platelet aggregation in vitro, with IC50 values of 8.90 x 10(-5), 1.50 x 10(-6) and 5.11 x 10(-8) mol/l, respectively. The strong inhibitory activity is significant not only for collagen but also for AA-induced aggregation. The same compound inhibits ex vivo collagen- and particularly AA-induced rabbit platelet aggregation at the tested dose of 10 mg/kg i.m. In view of the potential use of 2-amino-1,2-benzisothiazolin-3-one as antithrombotic agent, the log P values for both 1,2-benzisothiazolin-3-one derivatives 1 and 2 are determined, to gain an understanding of the significance of the 2-amino group in the 1,2-benzisothiazolin-3-one moiety with respect to the biological activity under study.
Vicini
P
P
Dipartimento Farmaceutico, Università di Parma, Italy.
Manotti
C
C
Caretta
A
A
Amoretti
L
L
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology*
C110132:2-amino-1,2-benzisothiazoline-3-one; D007202:Indicators and Reagents; D010975:Platelet Aggregation Inhibitors; D013844:Thiazoles; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; C015699:1,2-benzisothiazoline-3-one