Studies on the protective effect of ebrotidine on experimental ulcers induced by non-steroidal anti-inflammatory drugs in healthy volunteers.
Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamid e, CAS 100981-43-9, FI-3542) is a new H2-receptor antagonist providing a new therapy for the prevention and healing of non-steroidal anti-inflammatory drugs-induced gastroduodenal lesions. Carbonic anhydrase is a zinc enzyme, 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 follows: 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 carbonic anhydrase was based on the colorimetric method of changing pH with the stopped-flow technique. In group A, ebrotidine reduced total gastric mucosal carbonic anhydrase activity by 62%; in group B, indometacin increased carbonic anhydrase activity in gastric mucosa by 138%; in group C, the combined treatment with ebrotidine plus indometacin decreased gastric mucosal carbonic anhydrase activity by 38%. The present study shows that, unlike ranitidine, ebrotidine, a competitive H2-receptor antagonist, is also a non-competitive inhibitor of carbonic anhydrase I and II. By antagonizing the activating effects of indometacin on gastric mucosal carbonic anhydrase, ebrotidine prevents mucosal lesions caused by anti-inflammatory drugs.
Puscas
I
I
Department of Gastroenterology, Simleu Silvaniei, Romania.
Puscas
C
C
Coltau
M
M
Torres
J
J
Márquez
M
M
Herrero
E
E
Fillat
O
O
Ortiz
J A
JA
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology; D006635:Histamine H2 Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D013844:Thiazoles; D002256:Carbonic Anhydrases; C075156:ebrotidine; D007213:Indomethacin