Effects of the new anti-ulcer drug nizatidine on prostaglandins in the rat gastric mucosa.

The effects of nizatidine (N-[2-[[[2-[(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2), a new histamine H2-receptor antagonist, on the content of prostaglandins (PGs) in the rat gastric mucosa at doses that inhibit basal gastric acid secretion were compared with those of two other histamine H2-receptor antagonists, cimetidine and ranitidine. Nizatidine did not inhibit basal gastric acid secretion at a dose of 0.4 mg/kg but showed dose-dependent inhibition at doses of 10, 30, and 100 mg/kg. This drug had no effects on the content of PG in the gastric mucosa when subcutaneously administered at doses of 0.4, 10, 30 and 100 mg/kg once daily for 5 days. Cimetidine and ranitidine administered at doses that markedly inhibit basal gastric acid secretion (250 and 100 mg/kg/d, respectively) had no effects on the content of PG in the gastric mucosa. On the other hand, nizatidine, cimetidine, or ranitidine at concentrations of 1-100 mumols/l did not inhibit in vitro PGE2 synthesis using sheep seminal vesicle microsomes. These results suggest that nizatidine did not affect in vitro PGE2 synthesis and even doses that markedly inhibit gastric acid secretion had no effects on the content of PGs in the gastric mucosa.