BM 13.177 (4-[2-(benzenesulfonamido)-ethyl]-
phenoxyacetic acid) is a representative of a new class of sulfonamidophenylcarboxylic
acids which possess platelet-inhibitory and anti-thrombotic activity and inhibits the contraction of rabbit aorta stimulated by PG endoperoxides and TXA2.
BM 13.177 5 mg/kg
body weight p.o. protected rabbits from arachidonate-induced
sudden death and greater than or equal to 10 mg/kg dose-dependently reduced the experimental
thrombus formation induced in the rabbit aorta by perivascular administration of
silver nitrate. In guinea-pigs, the
collagen-induced bronchoconstriction was inhibited in a dose- and time-dependent fashion. The formation of TXA2 and the TXA2-induced platelet aggregation and smooth muscle contraction are probably crucial events in these experimental models. The protective effect of
BM 13.177 may, therefore, be due to the TXA2-antagonizing effect of
BM 13.177, which has been conclusively demonstrated in human platelets (PATSCHEKE and STEGMEIER,
Thrombosis Res., 33, 277-288 (1984). The antagonism of TXA2 is supported by the observation that
BM 13.177 also specifically inhibits the contraction of isolated arterial strips from rabbits which were stimulated with the
thromboxane A2 mimetic
U 46619. Schild-plot with a slope close to unity suggests a competitive type of antagonism.
BM 13.177 exhibited neither anti-inflammatory nor
ulcer-inducing activity of
cyclooxygenase inhibitors. Furthermore it did not block the TXB2 formation in spontaneously clotting blood from rabbits and did not inhibit the release of
prostacyclin-like activity from rabbit aortas. The lack of toxicological effects in long-term toxicity studies in rat and dog, together with the absence of objective and subjective side effects in the first human studies have encouraged us to initiate clinical trials in order to evaluate the therapeutic benefit of this new approach in humans.