M&B 28,767: A potent anti-secretory and anti-ulcer PG analogue a comparative study with 16, 16′ dimethyl PGE 2 methylester

Abstract

M&B 28,767 [(±)11-deoxy-16-phenoxy-ω-tetranor PGE 1] and 16, 16′-dimethyl PGE 2 methylester (DMPG) were compared for their effects on gastric acid secretion (GAS) and gastric ulceration (GU), employing various laboratory models. In anaesthetised rats, GAS was stimulated by a continuous i.v. infusion of pentagastrin (30 >g/kg/h), and PG analogues were perfused through the stomach for 1 h. M&B 28,767 (3–15 >g/kg/h) and DMPG (3–60 >g/kg/h) reduced GAS in a dose-related manner, the ED50 values being 4 and 15 >g/kg/h respectively. In conscious rats possessing indwelling gastric cannulae, oral doses of M&B 28,767 (0.025–0.1 >g/kg) and DMPG (0.50–1.0 >g/kg) caused a prolonged inhibition of pentagastrin-stimulated GAS. M&B 28,767 was 17 times more potent than DMPG; the respective ED50 values were 0.036 and 0.6 >g/kg. Indomethacin-induced ulceration in rats, was reduced by both M&B 28,767 and DMPG; the respective ED50 values being 3.0 and 0.8 >g/kg. Both compounds given orally increased gastrointestinal motility in mice; M&B 28,767 (1–3 mg/kg) and DMPG (0.1–0.3 mg/kg) caused diarrhoea, the former being about 0.1 times as potent as the latter. In another test, M&B 28,767 (0.5–5.0 mg/kg) and DMPG (10–40 >g/kg) overcame morphine-induced constipation in a dose-related manner, the respective ED50s being 0.9–1.4 mg/kg and 20–40 >g/kg. Thus, M&B 28,767 had a better profile of activity than DMPG as an antisecretory and antiulcer agent.