The antiplatelet and antithrombotic activities of
LCB 2853 (
sodium 4-[[1-[[[(4-chlorophenyl)sulfonyl]amino]methyl]cyclopentyl] methyl]benzeneacetate, CAS 141335-11-7) a novel
thromboxane A2 (TXA2) receptor antagonist were examined after
intravenous administration. The correlation between
LCB 2853 plasma concentration and ex vivo inhibition of
arachidonic acid-induced aggregation was observed in rats, for 4 h, as long as
LCB 2853 was detected in plasma by HPLC analysis. Pharmacokinetic parameters were determined. The antithrombotic activity was tested in arterial and
venous thrombosis models. In dog
coronary stenosis,
LCB 2853 shown a very high efficacy (ED50 = 7.2 micrograms/kg), whereas
acetylsalicylic acid (ASA) was only active at 3.2 mg/kg and
ticlopidine was ineffective at 12.8 mg/kg. In rat
venous thrombosis induced by combination of venous injury and blood stasis, perfused
LCB 2853 decreased the weight of thrombi in a dose related manner (ED50 = 220 micrograms/kg/min). In a comparative study, at 250 micrograms/kg/min,
ticlopidine was less potent and ASA failed to show any protection. The potent immediate efficacy of
LCB 2853 and the advantageous comparisons with ASA (which was ineffective in some models) or
ticlopidine (which needs metabolization lag time) observed in many models suggest that this compound may have beneficial effects in patients with TXA2-associated disturbances.