Beil W, Eltze M, Heintze K, Klemm K, Riedel R, Schudt C, Sewing K F, Simon A
Br J Pharmacol. 1986 Jun;88(2):389-95. doi: 10.1111/j.1476-5381.1986.tb10215.x.
The antisecretory action of the benzimidazole sulphoxide derivative B 823-10, 2[(4-methoxy-3-methyl-2-pyridylmethyl)-sulphinyl]- 5-trifluoromethyl(1H)-benzimidazole, was compared with the effect of the corresponding sulphide B 823-08 in several in vivo and in vitro and in vitro test systems. The sulphide B 823-08 and the sulphoxide B 823-10 were found to be equipotent in the Shay rat. The sulphide was found to inhibit H+ secretion in intact rabbit gastric glands and enriched guinea-pig parietal cells with lower potency than the corresponding sulphoxide. The relative potency in antisecretory activity (sulphide/sulphoxide) decreased in the following rank order: Shay rat: gastric glands: parietal cells. Purified K+/H+-ATPase was not blocked by the sulphide, whereas the sulphoxide inhibited the overall as well as the partial reactions of this enzyme. In all in vitro systems tested, inhibition of H+ secretion and enzyme activity by the sulphoxide, but not by the sulphide, was antagonized by SH-compounds such as dithiothreitol. It is concluded that in vivo sulphoxidation of the sulphide plays an important role in acid inhibition. In vitro an additional inhibitory mechanism of the sulphide has to be considered.
将苯并咪唑亚砜衍生物B 823 - 10（2 - [(4 - 甲氧基 - 3 - 甲基 - 2 - 吡啶基甲基) - 亚磺酰基] - 5 - 三氟甲基(1H) - 苯并咪唑）的抗分泌作用与相应的硫化物B 823 - 08在多种体内、体外测试系统中的作用进行了比较。发现硫化物B 823 - 08和亚砜B 823 - 10在 Shay 大鼠中效力相当。发现硫化物抑制完整兔胃腺和富集豚鼠壁细胞中H⁺分泌的效力低于相应的亚砜。抗分泌活性的相对效力（硫化物/亚砜）按以下顺序降低：Shay 大鼠＞胃腺＞壁细胞。纯化的K⁺/H⁺ - ATP酶未被硫化物阻断，而亚砜抑制该酶的整体及部分反应。在所有测试的体外系统中，亚砜而非硫化物对H⁺分泌和酶活性的抑制作用被二硫苏糖醇等 SH 化合物拮抗。得出的结论是，硫化物在体内的亚砜化在酸抑制中起重要作用。在体外，必须考虑硫化物的另一种抑制机制。
