M&B 28,767: a potent anti-secretory and anti-ulcer PG analogue. A comparative study with 16, 16' dimethyl PGE2 methylester.
M&B 28,767 [(+/-)11-deoxy-16-phenoxy-omega-tetranor PGE1] and 16, 16'-dimethyl PGE2 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 micrograms/kg/h), and PG analogues were perfused through the stomach for 1 h. M&B 28,767 (3-15 micrograms/kg/h) and DMPG (3-60 micrograms/kg/h) reduced GAS in a dose-related manner, the ED50 values being 4 and 15 micrograms/kg/h respectively. In conscious rats possessing indwelling gastric cannulae, oral doses of M&B 28,767 (0.025-0.1 microgram/kg) and DMPG (0.50-1.0 microgram/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 microgram/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 micrograms/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 micrograms/kg) overcame morphine-induced constipation in a dose-related manner, the respective ED50s being 0.9-1.4 mg/kg and 20-40 micrograms/kg. Thus, M&B 28,767 had a better profile of activity than DMPG as an antisecretory and antiulcer agent.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D003248:Constipation / Q000139:chemically induced; D003967:Diarrhea / Q000139:chemically induced; D005744:Gastric Acid / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D011459:Prostaglandins E, Synthetic; D009020:Morphine; C032405:11-deoxy-16-phenoxy-17,18,19,20-tetranorprostaglandin E1; D010418:Pentagastrin; D000527:Alprostadil; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin