生物活性

• 描述Proton pump inhibitors (PPIs) are now widely used for treatment of both erosive and non-erosive gastro-esophageal reflux disease (GERD and NERD). Tenatoprazole belongs to the class of covalent proton pump inhibitors and inhibits gastric H⁺, K⁺ -ATPase with potency similar to omeprazole(IC₅₀ = 6.2 μM for tenatoprazole and 4.2 μM for omeprazole, respectively). Tenatoprazole binds at the catalytic subunit of the gastric acid pump with a stoichiometry of 2.6 nmol/mg of the enzyme in vitro. In vivo, maximum binding of tenatoprazole was 2.9 nmol/mg of the enzyme at 2 h after IV administration. Further, the stability of inhibition and the long plasma half-life of tenatoprazole resulted in prolonged inhibition of acid secretion as compared to omeprazole^[1]. TU-199 inhibited basal gastric acid secretion in pylorus-ligated rats in a dose-dependent manner (ED₅₀ = 4.2 mg/kg p.o.). In gastric fistula rats, TU-199 (2.5 and 5 mg/kg i.d.) also inhibited gastric acid secretion stimulated by histamine, carbachol or tetragastrin. Furthermore, TU-199 prevented the formation of water-immersion restraint stress-, pylorus ligation- and indomethacin-induced gastric lesions, and mepirizole-induced duodenal ulcer in rats^[2].
• 作用机制The binding sites of tenatoprazole were in the TM5/6 region at Cys813 and Cys822 as shown by tryptic and thermolysin digestion of the ATPase labeled by tenatoprazole^[1].