Gastroprotective and ulcer-healing activities of a new H2-receptor antagonist: ebrotidine.
Ebrotidine is a novel H2-receptor antagonist that exhibits both gastroprotective and ulcer-healing properties. Gastroprotection afforded by ebrotidine against ethanol damage was observed only after intragastric, but not parenteral administration, and it was accompanied by an increase in the mucosal blood flow. Ranitidine given at the same dose (100 mg/kg i.g. or s.c.) did not show any protective activity. When administered twice daily at various doses (1-100 mg/kg) for 10 days, ebrotidine reduced dose dependently the area of chronic gastric ulcers, and it was accompanied by significantly higher contents of epidermal growth factor (EGF) in the ulcer bed than in the intact mucosa. Administration of ranitidine resulted in a similar rate of ulcer healing and in a similar accumulation of EGF in the ulcer area to that observed after ebrotidine, but the increments in plasma gastrin levels in rats treated with ranitidine were observed at lower doses than in tests with ebrotidine. Concurrent administration of indomethacin delayed ulcer healing and reduced the accumulation of EGF in the ulcer area, but did not affect the ulcer healing by ebrotidine or ranitidine. We conclude that ebrotidine but not ranitidine shows gastroprotective activity, but it enhances the healing of chronic ulcerations in a similar manner to ranitidine.
Brzozowski
T
T
Institute of Physiology, University Medical School, Krakow, Poland.
Majka
J
J
Konturek
S J
SJ
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D004815:Epidermal Growth Factor / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D005755:Gastrins / Q000097:blood; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D008297:Male; D011899:Ranitidine / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013276:Stomach Ulcer / Q000188:drug therapy*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*
D000085:Acetates; D001557:Benzenesulfonates; D005755:Gastrins; D006635:Histamine H2 Antagonists; D013844:Thiazoles; D000431:Ethanol; D004815:Epidermal Growth Factor; D011899:Ranitidine; D019342:Acetic Acid; C075156:ebrotidine