Description
Seratrodast, a novel benzoquinone derivative, is the first thromboxane A
2
(TxA
2) receptor antagonist to reach the market. It is orally active for the treatment of
bronchospastic disorders such as asthma. TxA
2, a metabolite of the arachidonate
cascade, is involved in several cardiovascular and respiratory diseases through its
potent biological effects on platelet aggregation and constriction of vascular and
respiratory smooth muscles. Seratrodast potently inhibits platelet aggregation and
bronchoconstriction induced by a TxA
2 mimic and by a variety of spasmogenic
prostanoids including PGF
2α, PGD
2 and 9α,11β-PGF
2. Seratrodast shows excellent
efficacy in asthma and has been reported to be potentially useful in hyper-responsive
disorder. The R-(+)- seratrodast was reported to be the active isomer.
Chemical Properties
Pale Orange Solid
Originator
Takeda (Japan)
Uses
Thromboxane A2-receptor antagonist. Antiasthmatic.
Definition
ChEBI: Seratrodast is an organic molecular entity.
Biological Activity
Thromboxane A 2 (TP) receptor antagonist. Antiasthmatic agent; inhibits platelet aggregation and bronchoconstriction induced by a TXA 2 mimetic in guinea pigs.
in vitro
seratrodast was found to inhibit the aggregation of guinea pig platelets induced by a prostaglandin endoperoxide analogue, u-44069 and the specific binding of another analogue, [3h]u-46619 to washed guinea pig platelets. seratrodast could competitively inhibit the contraction of rabbit aorta and pig coronary arteries induced by u-44069. seratrodast also inhibited the contraction of rabbit aorta induced by pgf2 alpha and the contraction of pig coronary arteries. however, seratrodast had no effect on the antiaggregatory effect of guinea pig platelets [1].
in vivo
in experiments with guinea pigs, oral seratrodast at 0.1-1 mg/kg could dose-dependently inhibit the platelet aggregation induced by u-44069; the inhibition at 1 mg/kg was 100% at 1 hr and was 89% even at 24 hr after seratrodast administration [1].
IC 50
7.4 nm for guinea pig platelets
References
[1] imura, y. ,terashita, z.,shibouta, y., et al. antagonistic action of aa-2414 on thromboxane a2/prostaglandin endoperoxide receptor in platelets and blood vessels. japanese journal of pharmacology 52(1), 35-53 (1990).
