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

Distinct Effects of Z-335, a New Thromboxane A₂ Receptor Antagonist, on Rabbit Platelets and Aortic Smooth Muscle

“…Our present study showed different affinity of Z-335 (pK i values) between platelets and aortic smooth muscle cells, while the affinities of [ 3 H]-SQ29548 (K d values) were similar between two tissues. Competitive binding study showed that the slope factor of Z-335 in pseudo Hill plotting in rabbit platelets was close to the value previously reported in human platelets [8] . However, the pseudo Hill factor of Z-335 was 0.38 in aortic smooth muscle cells, suggesting that Z-335 bound more than one binding sites in aorta.…”

“…This compound has been reported to be a potent, orally active and long-lasting inhibitor to platelet aggregation [8] . In this study, we showed that Z-335 had higher efficacy than SQ29548 in inhibition of platelet shape change and aortic constriction.…”

“…Our previous report has shown that SQ29548 inhibited both shape change and aggregation of rabbit platelets induced by U46619, a TP agonist, with similar potency, while ONO NT-126 showed more selective inhibition of platelet aggregation than shape change [7] . However, the precise mechanisms for the dif- A novel TP antagonist, ( 8 )-sodium[2-(4-chlorophe nylsulfonylaminomethyl)indan-5-yl]acetate monohydrate (Z-335) has been shown to be effective for U46619-induced platelet aggregation and arachidonic acid-induced hind limb gangrene as an orally active and long-lasting TP antagonist [8][9][10] . Although Z-335 inhibited U46619-induced platelet aggregation with nearly equal potency to another TP antagonist, daltroban, it inhibited U46619-induced vasoconstriction with over ten times potency than daltroban [11] .…”

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

“…11). A benzenesulfonamido moiety present in I-SAP features in simpler TP antagonist molecules, such as BM-13505 (daltroban; Yanagisawa et al, 1987), Z-335 (Tanaka et al, 1998) and S-18886 (terutroban; Fig. 11) (Cimetière et al, 1998) the distance from the C1-carboxylate group seems to be critical.…”

Thromboxane-prostanoid receptor expression and antagonism in dextran-sodium sulfate-induced colitis

“…The mice were given water ad libitum that was filter purified (Millipore Corp., Bedford, MA, USA) with or without addition of 5% (wt/vol) DSS (40 kD; ICN Biomedicals; Aurora, OH, USA) for 6 days. In some experiments, the drinking water also contained either the thromboxane synthase inhibitor ozagrel (25 mg/kg/day; Sigma Chemical; St. Louis, MO, USA) or the TP receptor antagonist vapiprost (2.5 mg/kg/day, Sigma), with these doses in the range of previous reports of their use [9][10][11].…”