Reference

Protective actions of a new thromboxane synthetase inhibitor in arachidonate-induced sudden death

Protective actions of a new thromboxane synthetase inhibitor in arachidonate-induced sudden death. Edmonds, Lee C.; Lefer, Allan M. (Jefferson Med. Coll., Thomas Jefferson Univ., Philadelphia, PA 19107, USA). Life Sci., 35(17), 1763-8 (English) 1984. CODEN: LIFSAK. ISSN: 0024-3205. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Section cross-reference(s): 1 A new thromboxane synthetase [61276-89-9] inhibitor, OKY-046 [78712-43-3], at 0.5 and 1.0 mg/kg prevented mortality induced by arachidonate [506-32-1] in 100% of the rabbits studied. Arachidonate at 1.25 mg/kg uniformly decreased mean arterial blood pressure to ~0 mm Hg, stopped respiration, and produced sudden death within 3-5 min in all rabbits studied. OKY-046 prevented all these sequelae. Untreated rabbits challenged with arachidonate develop large increases in circulating thromboxane B2 (TxB2) [54397-85-2] and 6-keto PGF1a [58962-34-8] of ~12- to 18-fold. In contrast, OKY-046 prevented the increase in TxB2 concns. and pulmonary thrombosis, but did not block the rise in 6-keto PGF1a following arachidonate injection. Apparently, the protective mechanism of OKY-046 in arachidonate-induced sudden death is via selective inhibition of thromboxane synthetase.

Effect of thromboxane synthetase inhibitors (OKY-046, OKY-1580) on the action of bronchoactive agents in guinea pig tracheal strips and on arachidonate metabolism in guinea pig lung lobes

Effect of thromboxane synthetase inhibitors (OKY-046, OKY-1580) on the action of bronchoactive agents in guinea pig tracheal strips and on arachidonate metabolism in guinea pig lung lobes. Kitamura, Satoshi; Ishihara, Yoko; Takaku, Fumimaro (Fac. Med., Univ. Tokyo, Tokyo 113, Japan). Prostaglandins, Leukotrienes Med., 14(3), 341-50 (English) 1984. CODEN: PLMEDD. ISSN: 0262-1746. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effect of the thromboxane synthetase [61276-89-9] inhibitors OKY-046 (I) [78712-43-3] and OKY-1580 (II) [75987-08-5] on the action of bronchoactive agents in guinea pig tracheal strips and on arachidonic acid [506-32-1] metab. in isolated perfused guinea pig lung lobes were investigated. OKY-046 and OKY-1580 attenuated histamine [51-45-6]-, serotonin creatinine sulfate [971-74-4]-, acetylcholine-chloride [60-31-1], bradykinin [58-82-2]-, and prostaglandin F2a [551-11-1]-induced contractile responses in guinea pig tracheal strips dose-dependently and potentiated isoproterenol [7683-59-2]-, salbutamol [18559-94-9]-, and prostaglandin E2 [363-24-6]-induced relaxation in guinea pig tracheal strips dose-dependently. In addn., OKY-046 and OKY-1580 inhibited the biosynthesis of thromboxane A2 [57576-52-0] and accelerated the prodn. of 6-keto prostaglandin F1a [58962-34-8] from arachidonic acid in isolated perfused guinea pig lung lobes. Thus, OKY-046 and OKY-1580 might be useful therapeutic agents for the treatment of pulmonary thromboembolism and chronic obstructive lung diseases.