MB 28,767: a potent anti-secretory and anti-ulcer PG analogue. A comparative study with 16, 16' dimethyl PGE2 methylester
| Autor: | M.A. Heazell, G.C. Ivers-Read, A.J. Christmas, K. Crowshaw, L.C. Saunders, A.K. Banerjee, D. Wyatt |
|---|---|
| Rok vydání: | 1984 |
| Předmět: |
Diarrhea
Male Prostaglandins E Synthetic Constipation Microgram Indomethacin Motility Pharmacology General Biochemistry Genetics and Molecular Biology Gastric Acid Mice 16 16-Dimethylprostaglandin E2 Medicine Animals Stomach Ulcer General Pharmacology Toxicology and Pharmaceutics Alprostadil ED50 Morphine business.industry Anti secretory Rats Inbred Strains General Medicine Rats Biochemistry Pentagastrin medicine.symptom business Gastrointestinal Motility |
| Zdroj: | Life sciences. 35(25) |
| ISSN: | 0024-3205 |
| Popis: | MB 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. MB 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 MB 28,767 (0.025-0.1 microgram/kg) and DMPG (0.50-1.0 microgram/kg) caused a prolonged inhibition of pentagastrin-stimulated GAS. MB 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 MB 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; MB 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, MB 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, MB 28,767 had a better profile of activity than DMPG as an antisecretory and antiulcer agent. |
| Databáze: | OpenAIRE |
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