Effect of ebrotidine on ethanol-induced gastric mucosal damage in the rat. Comparative study with other H2-receptor antagonists.
Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl ] amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is a novel H2-receptor antagonist with additional gastroprotective effect. The gastroprotective effect of oral doses of ebrotidine against ethanol-induced mucosal damage in female rats was compared with the effect of cimetidine, ranitidine and famotidine. Macroscopically, ebrotidine showed dose-dependent inhibition of the lesion, with significant differences from that of controls at doses of > or = 12.50 mg/kg (ED50 was 26.54 mg/kg). None of the other drugs tested showed gastroprotective effect under the same conditions. The histopathological study revealed significant reduction in the number of deep and superficial ulcers in ebrotidine-treated animals. The gastroprotective effect of ebrotidine is patent even in the presence of indometacin suggesting that prostaglandins play a rather negligible role in gastroprotective action. These results suggest that ebrotidine may be more useful than the classically known H2-antagonists in the treatment of peptic ulcers.
Palop
D
D
Centro de Investigación Farmacéutica Grupo Ferrer, Barcelona, Spain.
Romero
A
A
Villamayor
F
F
Conejo
L
L
Sacristán
A
A
Ortiz
J A
JA
D000818:Animals; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000494:pharmacology*; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D013844:Thiazoles; D000431:Ethanol; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine; C075156:ebrotidine; D007213:Indomethacin