Pharmacodynamics Study Of (-)-Pantoprazole Magnesium

Pantoprazole (PAN) is a proton pump inhibitor that is administered as a racemic mixture. It's one of the first-choice medicines when given to treat the acid-related gastrointestinal disorders such as reflux esophagitis, duodenal and gastric ulcer in clinic.The research of (-)-PAN-Mg demonstrated the action of anti-ulcer and suppressing the acid secretion through the experiments on intact animals and isolated organs, compared with (+)-PAN-Mg and (?-PAN-Mg.The results showed that (-)-PAN-Mg had obvious effect on water immersion restraint stress-induced gastric lesions in mice at the dose of 1.5 mg-kg-1, and the inhibition rate was 49.2%; but at the same dose, (+)-PAN-Mg and ( )-PAN-Mg had no marked difference compared with control group. Obviously inhibition rates were obtained with (-)-PAN-Mg compared with (+)-PAN-Mg and ( )-PAN-Mg on aspirin, reserpine -induced gastric ulcer in mice. (-)-PAN-Mg could decrease the gastric ulcer index remarkably in pylorus-ligated, ethanol-induced ulcer model and the duodenal ulcer index induced by cysteamine in rats. It was found that (-)-PAN-Mg had marked inhibitory effect on reflux esophagitis rats and histamine-induced gastric ulcer in guinea-pigs. Administration of (-)-PAN-Mg for 7 days obviously accelerated the healing ofacetic acid-induced gastric and duodenal ulcers, and the healing effect was obvious at 1.5, 3.0, 9.0mg-kg-1-d-1, p.o., so did (+)-PAN-Mg and ( )-PAN-Mg. But their potency was less than that of (-)-PAN-Mg. (-)-PAN-Mg could inhibit gastric acid secretion in rats in vivo and in vitro. In the model of acute fistula rats, (-)-PAN-Mg was about 15 and 3 times more potent than (+)-PAN-Mg and ( )-PAN-Mg, respectively. The IC50 values of (-)-PAN-Mg, (+)-PAN-Mg and ( )-PAN-Mg were 6.67 10-7, 2.46 10-6 and 9.99 10'7 mol-L'1 in the isolated gastric mucosa in guinea-pigs, respectively. (-)-PAN-Mg remarkably inhibited the basal gastric acid secretion and the gastric acid secretion induced by histamine of isolated rats stomach. Compared with control group, (-)-PAN-Mg had no obvious effect on the levels of PGE2, free mucus and barrier mucus of pylorus-ligated rats.The results indicated that (-)-PAN-Mg was superior to (+)-PAN-Mg and ( )-PAN-Mg in peptic ulcer, and the mechanism focuses on inhibiting gastric acid secretion.