STUDIES ON THE PROTECTIVE EFFECT OF EBROTIDINE ON EXPERIMENTAL ULCERSINDUCED BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS IN HEALTHY-VOLUNTEERS

Ebrotidine ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 1009 81-43-9, FI-3542) is a new H-2-receptor antagonist providing a new the rapy for the prevention and healing of non-steroidal anti-inflammatory drugs-induced gastroduodenal lesions. Carbonic anhydrase is a zinc en zyme, and its isozyme (carbonic anhydrase II) in parietal cells plays a central role in HCl secretion. The effects of ebrotidine on carbonic anhydrase in human subjects are reported. Eighteen healthy volunteers were distributed in 3 equal subgroups and treated for 10 days as foll ows: ebrotidine 800 mg/d p.o. (Group A); indometacin 4 mg/kg/d p.o. in 3 divided doses (Group B); ebrotidine 800 mg/d p.o. plus indometacin 4 mg/kg/d p.o. (Group C). Assessment of the enzymatic activity of carb onic anhydrase was based on the colorimetric method of changing pH wit h the stopped-flow technique. In group A, ebrotidine reduced total gas tric mucosal carbonic anhydrase activity by 62%; in group B, indometac in increased carbonic anhydrase activity in gastric mucosa by 138%; in group C, the combined treatment with ebrotidine plus indometacin decr eased gastric mucosal carbonic anhydrase activity by 38%. The present study shows that, unlike ranitidine, ebrotidine, a competitive H-2-rec eptor antagonist, is also a non-competitive inhibitor of carbonic anhy drase I and II. By antagonizing the activating effects of indometacin on gastric mucosal carbonic anhydrase, ebrotidine prevents mucosal les ions caused by antiinflammatory drugs.