Toshihisa Ushiro, Yasuhiro Tsukimi (*) and Hironori Tanaka
First Department of New Drug Research Laboratories, Technical Center, Shin Nippon Pharmaceutical Inc., 370 Mita, Kishiwada, Osaka 596, Japan
(*) To whom correspondence should be addressed.
Abstracr: We investigated the effect of a newly synthesized compound, 3-amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridine (SPI-447), on the activity of H+,K+-ATPase isolated from porcine gastric mucosa. In lyophilized gastric vesicles, SPI-447 inhibited K+-stimulated ATPase activity in a dose-dependent manner in a pH 7.4 solution (IC50=4.2 microM (1.05 - 16.8)). The inhibitory action of SPI-447 was enhanced at pH 6.8 (IC50=1.05 microM (0.31 - 3.57)) and not influenced by glutathione. In intact gastric vesicles, SPI-447 had no effect on the spontaneous diffusion of H+ across the microsomal membrane. These results indicate that SPI-447 directly inhibits gastric H+,K+-ATPase activity in a SH group-independent manner.
Keywords: H+,K+-ATPase, Anti-ulcer drug, SPI-447