舒洛芬及其他非麻醉性镇痛药对前列腺素前体在离体组织和血小板上作用的抑制作用。

Inhibition by suprofen and other non-narcotic analgesic drugs of the effects of prostaglandin precursor on isolated tissues and platelets.

作者信息

Van Nueten J M, Hoebeke J, De Clerck F, Awouters F, Janssen P A

出版信息

Arch Int Pharmacodyn Ther. 1976 Apr;220(2):297-310.

Abstract

Contractions caused by Slow Reacting Substance C(SRS-C) and by Arachidonic Acid hydroperoxide (AAP) in the guinea-pig ileum and by AAP in the rat fundus were studied in the presence of suprofen and of 3 reference compounds. The dose-related inhibitions were not due to antagonism of prostaglandins. Other agonists of gastrointestinal smooth muscle were not or only weakly antagonized. For the study of selective inhibition of AAP-induced contractions by non-narcotic analgesics, the rat fundus is the preferred preparation. In this model suprofen had an ED50 of 1.27 x 10(-7) M (0.033 mug/ml), being 1.5, 94 and 2, 020 times more potent than indomethacin, phenybutazone and acetylsalicylic acid, respectively. Suprofen also strongly inhibited malondialdehyde formation by guinea-pig platelets incubated with arachidonic acid. The reported effects point to inhibition by suprofen of prostaglandin biosynthesis. The antagonism of AAP-induced contractions in the rat fundus is a valuable test system for inhibitors of prostaglandin biosynthesis.

摘要

在舒洛芬及3种参比化合物存在的情况下，研究了豚鼠回肠中由慢反应物质C（SRS-C）和花生四烯酸氢过氧化物（AAP）引起的收缩以及大鼠胃底中由AAP引起的收缩。剂量相关的抑制作用并非由于对前列腺素的拮抗作用。胃肠道平滑肌的其他激动剂未被拮抗或仅被微弱拮抗。为研究非麻醉性镇痛药对AAP诱导收缩的选择性抑制作用，大鼠胃底是首选的制备标本。在该模型中，舒洛芬的半数有效剂量（ED50）为1.27×10⁻⁷ M（0.033 μg/ml），分别比吲哚美辛、保泰松和乙酰水杨酸强1.5倍、94倍和2020倍。舒洛芬还强烈抑制与花生四烯酸一起孵育的豚鼠血小板中丙二醛的形成。所报道的这些作用表明舒洛芬对前列腺素生物合成具有抑制作用。大鼠胃底中AAP诱导收缩的拮抗作用是前列腺素生物合成抑制剂的一个有价值的测试系统。