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Antiasthmatic activity of a novel thromboxane A2 antagonist, S-1452, in guinea pigs.
Int Arch Allergy Immunol. 1992; 98(3):239-46.IA

Abstract

We examined the effect of a potent thromboxane (Tx) A2 receptor antagonist, calcium (1R, 2S, 3S, 4S)-(5Z)-7-(((phenylsulfonyl)amino)bicyclo[2.2.1] hept-2-yl)-5-heptenoate dihydrate (S-1452), on antigen- and various allergic-spasmogen-induced contractions of guinea pig lung parenchymal strips and on the increase in insufflation pressure, an index of bronchoconstriction, in anesthetized guinea pigs. In isolated guinea pig lung parenchymal strips, S-1452 showed competitive antagonism of the contractile activity of U-46619, a TxA2 mimetic, with a pA2 value of 8.9. The compound also inhibited the contraction induced by prostaglandin (PG) D2 and PGF2 alpha, but a TxA2 synthetase inhibitor, OKY-046, did not. In contrast, both drugs inhibited not only leukotriene (LT) D4-induced contraction but also antigen-induced contraction in the presence of a histamine antagonist. In anesthetized guinea pigs, oral administration of S-1452 markedly inhibited the bronchoconstrictions induced by intravenous injection of U-46619, PGD2, PGF2 alpha, LTD4 and platelet-activating factor (PAF) with ED50 values of 0.006, 0.031, 0.112, 0.033 and 0.115 mg/kg, respectively, but OKY-046 inhibited only that by LTD4 and PAF. Additionally, bronchoconstriction following intravenous injection of antigen was almost completely suppressed by S-1452 (0.1 mg/kg) and partially by OKY-046 (300 mg/kg) in passively sensitized guinea pigs which were treated with diphenydramine and propranolol. The inhibitory effect of S-1452 against U-46619-induced broncho-constriction persisted up to 7 h after oral administration.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1392626

Citation

Arimura, A, et al. "Antiasthmatic Activity of a Novel Thromboxane A2 Antagonist, S-1452, in Guinea Pigs." International Archives of Allergy and Immunology, vol. 98, no. 3, 1992, pp. 239-46.
Arimura A, Asanuma F, Kurosawa A, et al. Antiasthmatic activity of a novel thromboxane A2 antagonist, S-1452, in guinea pigs. Int Arch Allergy Immunol. 1992;98(3):239-46.
Arimura, A., Asanuma, F., Kurosawa, A., & Harada, M. (1992). Antiasthmatic activity of a novel thromboxane A2 antagonist, S-1452, in guinea pigs. International Archives of Allergy and Immunology, 98(3), 239-46.
Arimura A, et al. Antiasthmatic Activity of a Novel Thromboxane A2 Antagonist, S-1452, in Guinea Pigs. Int Arch Allergy Immunol. 1992;98(3):239-46. PubMed PMID: 1392626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiasthmatic activity of a novel thromboxane A2 antagonist, S-1452, in guinea pigs. AU - Arimura,A, AU - Asanuma,F, AU - Kurosawa,A, AU - Harada,M, PY - 1992/1/1/pubmed PY - 1992/1/1/medline PY - 1992/1/1/entrez SP - 239 EP - 46 JF - International archives of allergy and immunology JO - Int. Arch. Allergy Immunol. VL - 98 IS - 3 N2 - We examined the effect of a potent thromboxane (Tx) A2 receptor antagonist, calcium (1R, 2S, 3S, 4S)-(5Z)-7-(((phenylsulfonyl)amino)bicyclo[2.2.1] hept-2-yl)-5-heptenoate dihydrate (S-1452), on antigen- and various allergic-spasmogen-induced contractions of guinea pig lung parenchymal strips and on the increase in insufflation pressure, an index of bronchoconstriction, in anesthetized guinea pigs. In isolated guinea pig lung parenchymal strips, S-1452 showed competitive antagonism of the contractile activity of U-46619, a TxA2 mimetic, with a pA2 value of 8.9. The compound also inhibited the contraction induced by prostaglandin (PG) D2 and PGF2 alpha, but a TxA2 synthetase inhibitor, OKY-046, did not. In contrast, both drugs inhibited not only leukotriene (LT) D4-induced contraction but also antigen-induced contraction in the presence of a histamine antagonist. In anesthetized guinea pigs, oral administration of S-1452 markedly inhibited the bronchoconstrictions induced by intravenous injection of U-46619, PGD2, PGF2 alpha, LTD4 and platelet-activating factor (PAF) with ED50 values of 0.006, 0.031, 0.112, 0.033 and 0.115 mg/kg, respectively, but OKY-046 inhibited only that by LTD4 and PAF. Additionally, bronchoconstriction following intravenous injection of antigen was almost completely suppressed by S-1452 (0.1 mg/kg) and partially by OKY-046 (300 mg/kg) in passively sensitized guinea pigs which were treated with diphenydramine and propranolol. The inhibitory effect of S-1452 against U-46619-induced broncho-constriction persisted up to 7 h after oral administration.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 1018-2438 UR - https://www.unboundmedicine.com/medline/citation/1392626/Antiasthmatic_activity_of_a_novel_thromboxane_A2_antagonist_S_1452_in_guinea_pigs_ L2 - https://www.karger.com?DOI=10.1159/000236191 DB - PRIME DP - Unbound Medicine ER -