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  • Title: Involvement of endogenous nitric oxide and sulfhydryl compounds in ebrotidine-induced gastroprotection.
    Author: Palop D, Conejo L, Sacristán A, Ortiz JA.
    Journal: Arzneimittelforschung; 1997 Apr; 47(4A):468-71. PubMed ID: 9205745.
    Abstract:
    The role of endogenous nitric oxide and sulfhydryl compounds in the prevention by ebrotidine (N-[(E)- [[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]amino] methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) (100 mg/kg i.g.) of ethanol-induced gastric damage in rats was demonstrated. When the animals were pretreated with N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, at the dose of 10 mg/kg i.v., the mucosal lesions were aggravated and the gastroprotective action of ebrotidine decreased from 85% to 24%. This decrease in ebrotidine protection was antagonized by L-arginine (200 mg/kg i.v.), the lesion inhibition rate being 69%. D-arginine (200 mg/kg i.v.) was ineffective and the inhibition afforded by ebrotidine was only 14%. Pretreatment with N-ethylmaleimide, a sulfhydryl blocker, at the dose of 50 mg/kg s.c., increased the mucosal lesion induced by ethanol, and the gastroprotective action of ebrotidine decreased from 75% to 9%. These results suggest that endogenous nitric oxide and sulfhydryl compounds play a crucial role in the gastroprotective activity of ebrotidine.
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