Tenatoprazole
Tenatoprazole (rINN, also benatoprazole) is a novel proton pump inhibitor indicated for the treatment of reflux oesophagitis and peptic ulcer in Japan. Discovered by Mitsubishi Pharma, it is an imidazopyridine derivative and has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors. It is activated more slowly than other proton pump inhibitors but its inhibition is resistant to reversal. Tenatoprazole has an extended plasma half-life in comparison with all other proton pump inhibitors; this makes it more potent and effective in the treatment of nocturnal acid breakthrough than esomeprazole, one of the most popular proton pump inhibitors.

# Pharmacological action
Tenatoprazole is a prodrug of the proton pump inhibitor (PPI) class, which is converted to the active sulfenamide or sulfenic acid by acid in the secretory canaliculus of the stimulated parietal cell of the stomach. This active species binds to luminally accessible cysteines of the gastric H+,K+ -ATPase resulting in disulfide formation and acid secretion inhibition. Tenatoprazole binds at the catalytic subunit of the gastric acid pump with a stoichiometry of 2.6 nmol mg(-1) of the enzyme in vitro. In vivo, maximum binding of tenatoprazole was 2.9 nmol mg(-1) of the enzyme at 2 h after IV administration. 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. Decay of tenatoprazole binding on the gastric H+,K+ -ATPase consisted of two components. One was relatively fast, with a half-life 3.9 h due to reversal of binding at cysteine 813, and the other was a plateau phase corresponding to ATPase turnover reflecting binding at cysteine 822 that also results in sustained inhibition in the presence of reducing agents in vitro. The stability of inhibition and the long plasma half-life of tenatoprazole should result in prolonged inhibition of acid secretion as compared to omeprazole. Further, the bioavailability of tenatoprazole was two-fold greater in the (S)-tenatoprazole sodium salt hydrate form as compared to the free form in dogs which is due to differences in the crystal structure and hydrophobic nature of the two forms.
Pharmacodynamic studies on the same subjects showed an increase of intragastric pH with tenatoprazole 40 mg daily for seven days significantly higher (p<0.05) than that observed with the same regimen of esomeprazole, the median pH being 4.60.9 and 4.20.8, respectively. In addition, the time spent above pH 4 during night-time after tenatoprazole administration was significantly longer than that observed with esomeprazole.  The intragastric pH during the night was similarly higher (4.71.1 Units with tenatoprazole and 3.61.4 Units with esomeprazole, p<0.01). The better control of intragastric acidity achieved with tenatoprazole during the night was already evident from the first 24-hour of dosing. 
A more recent pharmacodynamic and pharmacokinetic investigation did confirm and extended previous data showing the prolonged duration of acid suppression with tenatoprazole. The proportion of healthy volunteers spending at least 16 h above pH 4 in the 24 h period was remarkably higher with tenatoprazole than with esomeprazole (81.5% versus 34.5%, p3 and pH>4 were significantly higher with tenatoprazole, indicating a sustained control of intragastric acidity with this novel PPI compared to esomeprazole. After 7 days repeated dosing the maximal plasma concentration of tenatoprazole was almost six times higher than that of esomeprazole while AUC was 32 times higher. A significant correlation between AUC and percentage of time intragastric pH>4 was observed with tenatoprazole not only during but also after stopping treatment.
In summary, the available studies point out both pharmacokinetic and pharmacodynamic advantages of tenatoprazole over esomeprazole. Since this last compound provides  amongst the members of the class - the most effective control of intragastric pH whatever the parameter considered, it is conceivable that tenatoprazole could similarly be better than the other existing PPIs. Tenatoprazole (as well as its S-isomer) then appears a promising PPI for the treatment of acid-related diseases, where it has the potential to address unmet clinical needs.